https://cancerneuro.science/new-blog daily 0.75 2021-07-21 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1537131727103-EUA0BVVBIXA20Z6J858O/Picture2.png Journal Club https://cancerneuro.science/new-blog/2021/7/21/student-jc-post-transcriptional-repression-of-circadian-component-clock-regulates-cancer-stemness-in-murine-breast-cancer-cells monthly 0.5 2021-07-21 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626879871830-XM62X2I08HAQ3FM55QUE/tudoran.jpg Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 1: Schematic of non-hierarchal (A) vs hierarchal model (B) explanations of cancer heterogeneity. Note in the hierarchal model, “cancer stem cells” divide in a way that produces both new variants and self- renews the stem cell type. The non-hierarchal model accumulates mutations after divisions that lead to heterogeneity. (Tudoran et al., 2016) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626882054298-MNEWIYSRI6DQXT6ZKXAT/Fig+10.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 10. (Ogino et al., 2021) Similar to Fig. 8 above, this figure assesses tumor size (A), metastasis (B), and metastasis growth (C), in each of which CLOCK supplemented cells grow slower and metastasize less. Panel D shows the abundance of miRNA-182 expression in tumor cells, further supporting the hypothesis that it may act in ALDH+ cancer cells to suppress CLOCK activity. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626881878658-QYTFIV6VSSSS0DOASPK9/Fig+9.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 9: Schematic of structure and function of miRNAs. miRNAs (orange) bind to mRNAs and inhibit their transcription by the ribosome, therefore stopping the associated protein from being expressed in the cell. Credit: Wikipedia; KelvinSong, Creative Commons. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626881183459-EKYJVUAEX4FJPVUTJLBB/Fig+6.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 6: (Ogino et al., 2021) 2E- growth rates of cancer cells with CLOCK supplemented are significantly lower than those without supplemented CLOCK, 2F- Spheroid growth assay, showing the cell population with CLOCK supplemented have fewer spheroids growing (spheroids appear blue on images to the left), and smaller spheroids than the cell population without CLOCK supplemented (bar graph accounts for number and size of spheroids). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626880422903-B6F5D04A2MVXWPDDQ057/fig+1b.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 2. (Ogino et al., 2021) Graphical representation of relative amounts of ALDH+ cells within the 4T1 cancer cell line. The above shows that cells with increased expression of CLOCK protein, a key circadian regulator, had the lowest relative expression of ALDH activity. This indicates the probability of CLOCK having some inverse role in regulation or connection to ALDH expression levels. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626880870660-62UEAIMS71LBBDE04C6S/Fig+4.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 4. (Ogino et al., 2021) Western blot (top) and bar graph schematic of mRNA levels, showing much higher mRNA and protein expression in CLOCK transduced cells. p84 is a control used to normalize protein expression. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626880705944-EZ7NTXQLWQIGCJ3OZPVT/fig3.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 3: (Ogino et al., 2021) Luciferase data showing the oscillatory circadian expression of CLOCK protein after transduction by the authors. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626882265561-D1BPZ7NO0I3Z1FVR5G3K/Fig+11.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Credit: Ogino et al., 2021 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626881376677-M7Z4HLL0IV54QWPKXYO2/Fig+7.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 7: (Ogino et al., 2021) A. Invasion assay of cancer cells showing that populations receiving the CLOCK supplement are much less invasive(left images), with quantitative r=confirmation of less area being occupied by CLOCK supplemented cancer lines. B. Spheroid invasion assay images, showing qualitative observations of much less invasion and protrusion occurring from the cell spheres supplemented with CLOCK (bottom images). C. Western blot analysis of endothelial (less invasive cell type) markers E-cadherin and Claudin1, seen to be expressed more in CLOCK supplemented cells (right) than non-supplemented counterparts(left). Additionally, cancer cells not supplemented with CLOCK exhibit higher expression of mesenchymal marker, Vimentin (more invasive type). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626879474039-8Y7378JTULD4D1ZKS1SP/pexels-photo-1537268-1.jpg Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Credit: Dana-Farber Cancer Institute https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626881048550-9DM83EGC16RYECUUCVQR/Fig+5.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 5 (Ogino et al., 2021) relative levels of mRNAs known to be associated with “stem-ness”. This figure shows how the cells supplemented with CLOCK have a much lower expression of “stem-ness factors”. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1626881587884-AA2TBQ5APHBPL0I5IUW0/Fig+8.png Journal Club - Student JC: Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells - Make it stand out Figure 8: (Ogino et al., 2021)- A. Measurements and images of tumor volume after cancer cell implantation in mouse models. CLOCK supplemented cancer cell lines are consistently smaller than non-supplemented counterparts. B. Immunohistochemistry staining of CLOCK supplemented (bottom) vs. non-supplemented cancer cell lines. Authors stained for Ki-67+ cells (appearing pink/red), which indicates cells preparing for division and is frequently used to assess cancer progression. As seen qualitatively in images to the left, and quantitatively on the bar graph to the right, CLOCK supplemented cells have lower Ki-67+ levels, which is associated with a less severe cancer. C. Images and quantitative analysis of metastasis to the lungs after cancer cell injection shows CLOCK supplemented cancer cells exhibit less lung metastasis. D. Assessment of growth of metastatic colonies isolated from mice after cancer cell injection indicate less growth occurs with CLOCK induced cancer lines. https://cancerneuro.science/new-blog/2021/6/29/guest-jc-chronic-circadian-disruption-modulates-breast-cancer-stemness-and-immune-microenvironment-to-drive-metastasis-in-mice monthly 0.5 2021-07-01 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1625148336950-AF4ZTLYUWSVRVX0W9Q4O/LB_1.png Journal Club - Student JC: Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice - Make it stand out Figure 1: a. Experimental timeline for evaluation of the effect of chronic jet lag on spontaneous mammary tumorigenesis in B6*FVB PyMT mice. b. Tumor growth monitoring using bioluminescence. c. Weight at sacrifice of mice in LD and JL conditions. d. Blood cell counts: total numbers of white blood cells and red blood cells in LD and JL mice. f. Timeline of tumor growth in total flux measured by in vivo bioluminescence imaging in LD or JL groups. g. Tumor burden (tumor to body weight ratio) as % in LD or JL conditions. (Source: Hadadi et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1625149873015-UPJM246N6UCC7HOCBUKL/LB_3.png Journal Club - Student JC: Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice - Make it stand out Figure 3. CRD increases the proportion of cancer stem cells (dark blue) and alters the tumour microenvironment by recruiting myeloid-derived suppressor cells (yellow), which creates a suppressive tumour immune microenvironment (TIME), which could relate to the enhanced CXCL5-CXCR2 axis in the TIME. These effects result in increased dissemination and metastasis in bone marrow and lungs. Inhibition of the CXCR2 axis is able to lighten the effect of CRD and promote anti-tumour activity. (Source: Hadadi et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1625149739096-VFVIJZNWSDZB8Z6OR7IH/LB_2.png Journal Club - Student JC: Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice - Make it stand out Figure 2. a. Representative gating strategies for mammary stem cells (MaSC) with contour plots shown for LD (black) and JL (red) tumors. b. Frequency of mammary stem cells in LD and JL tumors. c. Mammosphere-formation efficiency of LD and JL tumor cells. (Source: Hadadi et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1625148585078-VCFSOLU4JQORDNIOGA6X/jetlag.png Journal Club - Student JC: Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice - Make it stand out (Credit: Bob Al-Greene/Mashable) https://cancerneuro.science/new-blog/2019/12/15/my-top-8-scientific-papers-of-2019 monthly 0.5 2019-12-31 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1577803854625-WYLTJP8IKPW87X0BLFNP/Screen+Shot+2019-12-31+at+9.50.05+AM.png Journal Club - My Top 5 'Coolest' Studies of 2019 A schematic of the neural ‘sewing machine’ for chronic recordings of diverse neural activities (credit: Hanson et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1577655358314-K1GQUF0MXETD16NU3XGG/Screen+Shot+2019-12-29+at+4.35.45+PM.png Journal Club - My Top 5 'Coolest' Studies of 2019 A schematic representation of neuroglioma synapses. Neurons form AMPA-receptor receptor dominated glutamatergic synapses with growing glioma cells. Synaptic stimulation causes activation (depolarization) of cancer cells and large increases in intracellular calcium. This signal is propagated throughout the glioma network via gap junctions linking cancer cells together (Credit: Venkataramani et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1577741819883-BQTS48SWC0P55W5VP2NO/Screen+Shot+2019-12-30+at+4.36.34+PM.png Journal Club - My Top 5 'Coolest' Studies of 2019 ER-alpha expressing neurons in the arcuate nucleus powerfully regulate bone density only in female mice. These findings offer a previously unknown target for the treatment of age-related bone disease. (Credit: Fields et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1577656000658-33YXENC7EEZDYCSSKS4Q/Screen+Shot+2019-12-29+at+4.43.00+PM.png Journal Club - My Top 5 'Coolest' Studies of 2019 Waves of aging proteins across the lifespan. Thousands of proteins show age-dependent changes in expression in blood, with peaks noted at age 34, 60 and 78 (credit: Lehallier et al., 2019). https://cancerneuro.science/new-blog/2019/11/3/stress-induced-metabolic-disorder-in-peripheral-cd4-t-cells-leads-to-anxiety-like-behavior monthly 0.5 2019-11-12 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1573584539855-O5MS919BQ70UO5YRKY49/Screen+Shot+2019-11-12+at+10.40.49+AM.png Journal Club - Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior Figure 5: Miga2 KO mice have increased numbers of oligodendrocytes in the left amygdala, and this is dependent on CD4+ T cells. Knockdown of the putative xanthine receptor AdorA1 (using shRNAs) on oligodendrocytes in the amygdala rescues anxiety-like behavior in the knockout mice. These findings link changes in peripheral immunity and purine metabolism to dysfunctional neural activity and the generation of stress-induced anxiety. (Credit: Fan et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1573451637977-ST7LWR0D36UW2KIYFY85/Screen+Shot+2019-11-10+at+9.53.30+PM.png Journal Club - Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior Figure 4: Stress-induced mitochondrial dysfunction in CD4+ T cells promotes anxiety via aberrant increases in xanthine production. Metabolic analyses of serum from WT and Miga2 T-cell KOs (Miga2TKO) revealed marked increases in purine metabolic pathways, and specifically xanthine (~1000x fold increase (10^3)! Xanthine infusions promoted the anxiety like behavior in mice and were drastically elevated in human patients with clinical anxiety. (Credit: Fan et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1573582512897-BTVLV8VBBY86Y5PWJ1BB/Screen+Shot+2019-11-10+at+9.50.40+PM.png Journal Club - Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior Figure 3: Disrupted mitochondrial function promotes anxiety-like behavior that depends on CD4+ T cell function. Knocking out the mitochondrial membrane protein Miga2 (Miga2-/-) produces severe anxiety-like behavior, which can be rescued by CD4+ T cell depletion. (Credit: Fan et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1572824176823-Y9LEICH7TVT0J6XTUQLQ/Screen+Shot+2019-11-03+at+3.35.27+PM.png Journal Club - Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior Figure 6: Summary of findings. Stress-induced elevations of LKB4 cause aberrant mitochondrial function in CD4+ T cells. This results in elevations in circulating xanthine levels which signal via A1 receptors on oligodendrocytes in the amygdala. This alters local neural activity to promote anxiety-like behavior! (Credit: Fan et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1573434571278-48L7E6X4JM6JFESIZINJ/Screen+Shot+2019-11-10+at+5.09.13+PM.png Journal Club - Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior Figure 1: CD4+ T cells play a major role in the development of stress-induced anxiety-like behavior. Mice were given injections of control antibody (IgG), anti-CD4, or anti-CD8 to deplete two major subtypes of T cells. IN a separate group, wild-type (WT) mice were compared to those lacking B and T cells (Rag1-/-). They were given daily electric footshocks (ES) for 8 days to elicit stress responses. A day later, mice were tested for the development of anxiety like behavior in an open field test. Rag-/- mice showed no anxiety like behavior following footshock stress (Panel B), and similarly, mice with their CD4+ T cells ablated also didn’t show anxiety like behavior (panel C). Credit: Fan et al., 2019 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1573435174397-UW38H8DBLWIL2EK5Q4RX/Screen+Shot+2019-11-10+at+5.19.16+PM.png Journal Club - Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior Figure 2: RNA-seq of T cells reveals altered gene expression in CD4+ T cells in response to chronic electric footshock stress (Panels A-D). These differentially expressed genes largely contribute to mitochondrial function. On tests of energy production, CD4+ T cells from stressed mice showed severely impaired glycolytic and oxidative phosphorylation capacity (Panel E). (Credit: Fan et al., 2019). https://cancerneuro.science/new-blog/2019/9/18/electrical-and-synaptic-integration-of-glioma-into-neural-circuits monthly 0.5 2019-10-10 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1570673070231-T9RCJ1KHEBSQ27MZ50N4/Screen+Shot+2019-10-09+at+7.04.13+PM.png Journal Club - Electrical and synaptic integration of glioma into neural circuits Figure 3: Neural activity drives glioma progression. (a,b,c,d) optogenetic stimulation of neurons in the tumor microenvironment promotes tumor growth/proliferation. (e,f,g,h) Over-expressing the AMPA receptor sub-unit GluA2 accelerates brain tumor lethality, and inhibiting GluA2 expression using a dominant negative approach suppresses brain tumor lethality! (i) shows us the big difference between mice with normal levels of GluA2 and those with a non-functioning dominant negative version. (j) Indeed, the tumor burden of mice with reduced AMPA receptor signaling (GluA2-DN-GFP) had a much lower tumor burden than their counterparts with normal levels. This effect was mirrored when AMPA receptor antagonists were used (e.g., Perampanel) instead of the transgenic approach. (Credit: Venkatesh et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1570672150564-WSMWCMITOY0FGKU10NG1/Screen+Shot+2019-10-09+at+6.47.05+PM.png Journal Club - Electrical and synaptic integration of glioma into neural circuits Figure 2: Glioma cells form functional glutamatergic synapses. Mice were transplanted with DIPG tumor cells into the hippocampus (shown in a schematic in (a)). Following some time to allow the tumor to integrate into the tissue, the researchers stimulated a pathway known as the “Schaffer collateral” pathway in the hippocampal CA1 region, which is a very well defined neural pathway in the brain. They recorded any responses to this stimulation in the tumor cells using a recording electrode. In (c-i) the authors demonstrate that stimulating this pathway causes depolarization (change in voltage) in the tumor cells. In (k,l,m) they demonstrate that when they use GCaMP recordings instead of electrophysiology, they can detect large changes in activity in tumor cells following stimulation! (Credit: Venkatesh et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1570674288674-4UOH22025AGQ4Z8VB92G/Screen+Shot+2019-10-09+at+7.24.31+PM.png Journal Club - Electrical and synaptic integration of glioma into neural circuits Figure 4: Neurons are extra-excitable in the glioma-infiltrated human brain! (Credit: Venkatesh et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1570476358422-E4WQI7YQNPDGW98QKH9V/Screen+Shot+2019-10-07+at+12.25.24+PM.png Journal Club - Electrical and synaptic integration of glioma into neural circuits Neural activity promotes tumor growth and progression. Glutamate signaling depolarizes (activates) tumor cells that are ‘listening in’ on normal neural communication. (Credit: Barria, 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1570671221130-HDNZCQRQC1J9MOJQ67E8/Screen+Shot+2019-10-09+at+6.30.43+PM.png Journal Club - Electrical and synaptic integration of glioma into neural circuits Figure 1: Evidence for functional synapses between neurons and brain tumor cells. In (a) we can see that the expression levels of synapse-related genes (GRIN1, GRIA1,2,3, GRIK2, DLG4, NLGN3, HOMER1) are highly enriched in malignant vs. non-malignant tissues from cancer patient samples. In (b) the data are arranged to see the lineage (x axis) and stemness (y axis) of cells from primary patient samples. In (c) we can see physical signs of synapses using electron microscopy in a human (left) and mouse (right) brain tumor. In (e) and (f) the researchers found signs of synaptic transmission in glioma by labeling the protein post-synaptic density-95 (PSD-95) and synapsin. (Credit: Venkatesh et al., 2019). https://cancerneuro.science/new-blog/2019/9/3/dopamine-signaling-controls-body-temperature-and-weight-in-rats-and-humans monthly 0.5 2019-09-06 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1567721244734-LA9YDW17HLSO7W5O59ZA/Screen+Shot+2019-09-05+at+3.04.18+PM.png Journal Club - Dopamine signaling and weight loss - Mechanistic insights from mice, rats, and humans Figure 2: The lateral hypothalamus/zona incerta is the primary brain area regulating systemic responses to bromocriptine (BC) treatment. Infusion of bromocriptine into the LH/ZI of rats had the same effect as brain-wide administration (Credit: Folgueira et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1567642138524-55TJCV5VFRYUO1TEMCD5/types+of+hunger.jpg Journal Club - Dopamine signaling and weight loss - Mechanistic insights from mice, rats, and humans Two major types of hunger drive different feeding behaviors (Credit: Karl Tate, livescience.com) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1567724610432-LA57FOZUGVHOWBPEB9DU/Screen+Shot+2019-09-05+at+3.59.18+PM.png Journal Club - Dopamine signaling and weight loss - Mechanistic insights from mice, rats, and humans Figure 3: DREADD-mediated activation of GABA-expressing neurons in the lateral hypothalamus/zona incerta repeat the effects seen with bromocriptine treatment. This suggests that GABA neurons in this hypothalamic area dictate the effect of dopamine signaling on whole-body metabolism and body weight (Credit: Folgueira et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1567706729419-I4SZHK6D1M3NGOSJMF21/Screen+Shot+2019-09-05+at+11.05.10+AM.png Journal Club - Dopamine signaling and weight loss - Mechanistic insights from mice, rats, and humans Figure 1: Enhancing D2R-mediated dopamine signaling in the brain (via bromocriptine infusions) reduces weight gain and influences brown adipose tissue (BAT) protein levels. This effect is driven largely by the sympathetic nervous system, as blocking beta-3 receptors blocks the effect of bromocriptine. (open circles = no bromocriptine infusion; green closed circles = bromocriptine infusion; grey closed circles = bromocriptine + beta-3 blocker infusion) (Credit: Folgueira et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1567732636005-AG9BTQPSGBDTJG0C22UR/Screen+Shot+2019-09-05+at+6.16.55+PM.png Journal Club - Dopamine signaling and weight loss - Mechanistic insights from mice, rats, and humans Figure 4: Humans treated with a dopamine D2R agonist, cabergoline, lost significant amounts of weight 3 months after treatment started. Above, you can see the data stratified to show per-patient responses. (Credit: Folgueira et al., 2019). https://cancerneuro.science/new-blog/2019/8/2/cd24-signalling-through-macrophage-siglec-10-is-a-target-for-cancer-immunotherapy monthly 0.5 2019-08-04 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1564879063845-9RABW62X4DO7ZAIA0ZJD/Screen+Shot+2019-08-03+at+5.37.24+PM.png Journal Club - CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy Figure 3: Blockade of tumor cell CD24 increases tumor cell destruction (phagocytosis) by preventing inhibitory siglec-10 signaling on macrophages. This effect is evident in models of breast, pancreatic, and small-cell lung cancer, but not in cells that naturally do not express CD24 (U-87 MG). Additionally, blockade of CD24 and CD47 drastically increases primary cancer cell destruction by patient derived macrophages in a patient with ovarian cancer. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1564954426775-IQW8OMDXHVM5OKT2MWOC/Screen+Shot+2019-08-04+at+2.33.25+PM.png Journal Club - CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy Figure 4: Cancer cells with mutated (non-functional) CD24 form smaller tumors which are less lethal than those formed by cells with functional CD24. Additionally, blocking CD24 with anti-CD24 antibodies resulted in smaller tumors similar to what was seen with genetic inactivation of CD24. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1564787141104-MCBDVMRVSCB6W0XN1ZS0/Immunotherapy.jpg Journal Club - CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy Cancer immunotherapy works by blocking ‘don’t eat me signals’ expressed by tumor cells. These signals (e.g., PD-L1) normally act to suppress adaptive immune responses, allowing cancer cells to escape destruction. If we block these signals, the immune system is no longer suppressed, and can recognize and kill the tumor. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1564871438601-T02DZY3XMM9FPBD0W31G/Screen+Shot+2019-08-03+at+3.30.15+PM.png Journal Club - CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy Figure 1: CD24 is widely expressed in many forms of cancer (in panel a), and its expression in ovarian and breast cancer is associated with poor prognoses (panels b and c). Additionally, CD24 is primarily expressed by tumor cells while Siglec-10, the binding partner for CD24, is primarily expressed by macrophages in the tumor microenvironment. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1564957254733-BK3FZDQQHKYYGBEYVQWJ/Screen+Shot+2019-08-04+at+3.20.36+PM.png Journal Club - CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy Figure 5: Mechanism of cancer cell destruction by tumor associated macrophage through blockade of CD24 - Siglec-10 signaling. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1564871503229-CAV4H7DUCL57GMTTUBEU/Screen+Shot+2019-08-03+at+3.31.29+PM.png Journal Club - CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy Figure 2: CD24 blockade (alone or in combo with CD47 blockade) significantly increases cancer cell destruction by macrophages. Similarly, knocking out the binding partner for CD24 (siglec-10) had similar effects. Note the number of red puncta in panel i, these indicate cancer cells that have been eaten (destroyed) by macrophages. There is much more red after CD24 is blocked. https://cancerneuro.science/new-blog/2019/6/30/transneuronal-propagation-of-pathologic-alpha-synuclein-from-the-gut-to-the-brain-models-parkinsons-disease monthly 0.5 2019-07-08 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1562550459136-724IPMKEK5AHA7UF9SH0/Screen+Shot+2019-07-07+at+9.47.18+PM.png Journal Club - Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease Summary of the study’s findings. In a ‘normal’ mouse, injection of pre-formed fibrils into the gut causes Parkinson’s disease-like symptoms and pathology. This can be prevented by cutting the vagus nerve or by knocking out the gene for alpha-synuclein (Snca-/-) (Credit: Ko et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1562366906918-J0FOTIOR9AB6KRUPF6CM/Screen+Shot+2019-07-05+at+6.48.11+PM.png Journal Club - Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease Injection of PFFs into the gut (pyloric stomach/duodenum) promotes the destruction of dopaminergic neurons in the mouse midbrain. Note the difference between the 7 and 10 month time-points between mice injected with PBS (control) or PFFs. Both dopaminergic (TH) and total (Nissl) neuron counts were drastically reduced by 7 months post-injection. Levels of TH, the dopamine transporter (DAT), and dopamine itself were significantly reduced by 7-10 months post-injection (Credit: Ko et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1562367240568-VPHC41MMI01W7LRRA48H/Screen+Shot+2019-07-05+at+6.53.44+PM.png Journal Club - Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease Trucal vagotomy (TV) or knockout of endogenous alpha-synuclein (Snca-/-) prevents the destruction of midbrian dopamine neurons characteristic of Parkinson’s disease! Note that alpha-synuclein aggregates (p-alpha-Syn; green color) were only observed in mice with intact vagal nerves and with normal copies of the Snca gene (Credit: Ko et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1561931340374-M9IQHPYCWUP57MWGKPVH/Screen+Shot+2019-06-30+at+2.48.10+PM.png Journal Club - Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease Pre-formed Fibrils (PFFs) injected into the pyloric stomach (PS) or upper duodenum (UD) promote synucleinopathy in multiple brain regions. The pathology spreads in a stereotypical pattern resembling Parkinson’s disease progression. Alpha-synuclein aggregates are shown as ‘brown spots’ in the photomicrographs above. Note that mice receiving a control injection (PBS) do not show any aggregates even at 10 months post-injection (Credit: Kim et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1561932078914-FF8VKLQGSJC4DMNJLILC/villa-medica-parkinsons-facts-sheet-infographic-2-compressor.jpg Journal Club - Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson's Disease An overview of Parkinson’s Disease. (Credit: Villa Medica) https://cancerneuro.science/new-blog/2019/5/19/progenitors-from-the-central-nervous-system-drive-neurogenesis-in-cancer monthly 0.5 2019-06-05 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559687584237-SYIYC1JD2XAYMZ2RWXIZ/FIg+4.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Figure 4: Neural progenitors in the brain (SVZ) migrate through the blood towards the prostate tumor in the Hi-MYC mouse model of pancreatic cancer. Note: red (TdTomato) cells that originated in the brain’s SVZ could be found in the tumor throughout tumor development! Credit: Mauffrey et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559511032990-6YM2DNI3SLO55GWEJ5UA/Fig+1.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Figure 1: Neural progenitors (DCX+, PSA-NCAM+, INA+) are found in prostate tumor samples and they provide a prognostic indicator of cancer recurrence/survival. These neural progenitors do not express markers of epithelial cells or mature neurons, and increased amounts of these cells within the tumor is associated with high-risk tumors compared to low-risk and benign (BPH) samples. Additionally, with each part of the prostate that the tumor invades, there is a concomitant increase in neural progenitor cells. (Credit: Mauffrey et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559696023774-0QEEGJGVZ48LP0WH7Q88/Fig+5.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Figure 5: DCX+ progenitor cells regulate tumor development in mice. Mice lacking DCX+ cells grew tumors that were much less aggressive and invasive. (Credit: Mauffrey et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559517447881-7C5P6L133XQK58GQ4YMC/neuro+progenitor.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Neural Progenitor Cells (DCX+, green), Astrocytes (GFAP+, blue), and blood vessels (CD31+, red) in the mouse olfactory bulb. These cells are born in the subventricular zone, and then migrate to the olfactory bulb along the rostral migratory stream to integrate into olfactory (smell) circuits. (Credit: CC; Oleg Tsupykov). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559513035103-WJNF8RVQEZZJO48VZ7J3/Fig+2.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Figure 2: In a mouse model of prostate cancer (Hi-MYC) where neural progenitor cells are labeled yellow (DCX-eYFP), these cells are found throughout the prostate, similar to DCX expression in human tumors. Additionally, these prostate DCX+ cells express markers of neural progenitors (e.g., nestin, CD24) without markers of stem cells (e.g., SOX2). (Credit: Mauffrey et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559514223107-2WK2B8Q10F3FKYQU2I3I/WW+JCB.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Tumors interact with their local environment and by extension, the whole organism. These interactions can result in deleterious outcomes for patients, like tumor progression, metabolic problems, anorexia, inflammation, and sleep/circadian disruption. Magnon and colleagues provide evidence that in addition to these established pathways, neural progenitor cells leave the brain and migrate to the tumor (in a model of prostate cancer), promoting cancer growth and progression. (credit: Walker II & Borniger, 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559684732588-3NCIKKHNZYZ18S9NHM3K/Fig+3.PNG Journal Club - Progenitors from the central nervous system drive neurogenesis in cancer Figure 3: Neural progenitors in the prostate differentiate into adrenergic neurons during tumor development. (Credit: Mauffrey et al., 2019) https://cancerneuro.science/new-blog/2019/4/28/exercise-enhances-motor-skill-learning-by-neurotransmitter-switching-in-the-adult-midbrain monthly 0.5 2019-05-02 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556827169237-LG5GMZHIU6KSML4YKKXK/Screen+Shot+2019-05-02+at+12.59.14+PM.png Journal Club - Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain Prevention of the Acetylcholine/GABA switch during training prevents motor learning. Using a short-hairpin targeting GAD1 (shGAD1) to knock down it’s expression in ChAT+ neurons in the PPN, the authors demonstrate that without increased levels of GABA in response to running, the mice no longer learn this task. (Credit: Li & Spitzer, 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556824812888-SCIEJ2JK9J1H5GUC1XNG/Screen+Shot+2019-05-02+at+12.19.57+PM.png Journal Club - Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain Running induces a neurotransmitter switch from acetylcholine to GABA in the caudal pedunculopontine nucleus (cPPN). Above, we can see that the number of acetylcholine producing neurons (ChAT+) decreases in response to running, with a concomitant increase in GABA-production (GAD1+). (Credit: Li & Spitzer, 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556826471471-Y443DYMFDZHG7MCZTJ7M/Screen+Shot+2019-05-02+at+12.47.35+PM.png Journal Club - Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain Viral-mediated prevention of neurotransmitter switching (via upregulation of ChAT expression) prevents motor learning following a running task. (Credit: Li & Spitzer, 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556502591393-1BW0O4S86L5GXIUDUL9S/Screen+Shot+2019-04-28+at+6.49.26+PM.png Journal Club - Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain One week of running training induces motor learning, an effect that lasts at least 2 weeks post-training. (Credit: Li & Spitzer, 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556825725421-H2UV5K5LTFWJ4IMJB9BU/Screen+Shot+2019-05-02+at+12.35.07+PM.png Journal Club - Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain Acetylcholine-expressing neurons in the caudal Pedunculopontine nucleus (cPPN) lose acetylcholine and gain GABA in response to 1 week of running training. (Credit: Li & Spitzer, 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556824185150-A8VXFXB1N5HY28ML6ZBP/Screen+Shot+2019-05-02+at+12.09.24+PM.png Journal Club - Exercise enhances motor skill learning by neurotransmitter switching in the adult midbrain Running induces neural activity (cFos labeling) in multiple brain regions, and most notably in the pedunculopontine nucleus (PPN). Here, we can see that in response to running, higher amounts of cFos are detected in the PPN (red = all neurons, green = cFos (active neurons)). (Credit: Li & Spitzer, 2019) https://cancerneuro.science/new-blog/2019/4/2/a-gut-to-brain-signal-of-fluid-osmolarity-controls-thirst-satiation monthly 0.5 2019-04-02 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1554236576936-V7HZDX4E97FPXLOOB6PB/Screen+Shot+2019-04-01+at+3.50.23+PM.png Journal Club - A gut-to-brain signal of fluid osmolarity controls thirst satiation The subfornical organ (SFO) rapidly reduces activity upon drinking either regular (Water) or salty (NaCl) water (panel b). However, when solutions of different salt concentrations (osmolarity) were directly infused into the gut (panel d), the SFO drastically increased its activity (panels e,f,g) as a function of the osmolarity of the solution (R^2 = 0.98; also known as a near 1 to 1 relationship). (note: F/F means ‘fractional fluorescent change’, indicating the activity of the cells being measured) (Credit: Zimmerman et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1554239457340-TK2069NRGC5N5RC0IWOS/Screen+Shot+2019-04-02+at+1.47.58+PM.png Journal Club - A gut-to-brain signal of fluid osmolarity controls thirst satiation Supraoptic nucleus (SON) vasopressin neurons are rapidly inactivated by drinking (panel C), and bidirectionally regulated by gut fluid osmolarity (panel d). The heat maps in (d) show the activity of these neurons where warmer colors represent higher activity. Note that increases in fluid salt content (150 mM to 500 mM) causes stepwise increases in neural activity. (Credit: Zimmerman et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1554240273015-UTDMI3NFGHIAB7U07MF7/Screen+Shot+2019-04-02+at+2.22.15+PM.png Journal Club - A gut-to-brain signal of fluid osmolarity controls thirst satiation Both in vivo microendoscopy (a) and fiber photometry (b) measure neural activity by collecting light emitted by a fluorescent genetically encoded calcium indicator in neurons of interest (e.g., GCaMP6s). More cumbersome and harder to use, the microendoscope technique allows researchers to examine the activity of individual cells over long periods of time in awake, behaving mice. This is a major advantage over fiber photometry, as it allows one to understand how different cells in the circuit act in response to various stimuli. (Credit: Resendez & Stuber, 2015). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1554235589801-JBNUA8TQRSM1RW3GKQ8N/Screen+Shot+2019-04-02+at+1.06.06+PM.png Journal Club - A gut-to-brain signal of fluid osmolarity controls thirst satiation Brain structures underlying thirst, drinking, and satiation. A major component is the subfornical organ (SFO), which receives input on the volume of fluid consumed, and directs changes in drinking behavior using excitatory (glutamate) and inhibitory (GABA) signaling. (Credit: Zimmerman et al., 2017) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1554240771879-UEVTALS30B8HGPLAAA94/Screen+Shot+2019-04-02+at+2.32.30+PM.png Journal Club - A gut-to-brain signal of fluid osmolarity controls thirst satiation GABA-producing neurons within the median preoptic nucleus (MnPO) can be clustered into “ingestion-activated”, “ingestion-inhibited”, or “untuned” based on their responses to fluid intake. in panel (d) we can clearly see segregation of these neural responses following drinking. (Credit: Zimmerman et al., 2019) https://cancerneuro.science/new-blog/2019/2/13/fish-hunting-cone-snail-venoms-are-a-rich-source-of-minimized-ligands-of-the-vertebrate-insulin-receptor monthly 0.5 2019-03-02 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551494805996-YYRHD7R6MTAB925PL1H1/Screen+Shot+2019-03-01+at+6.37.15+PM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae Photoreceptor-binding Up-Conversion NanoParticles (pbUNCPs) bind to natural photoreceptors (rods and cones). Above, you can see that when mice were injected with just PBS, no pbUCNP signal is observed…however when they are injected with PBS + pbUCNPs….the nanoparticles latch onto existing rods and cones, showing that they can ‘hijack’ or ‘co-opt’ normal visual pathways in the retina (Ma et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551555070145-W9HQ2A20T2DR37I9ABHO/Screen+Shot+2019-03-02+at+11.30.47+AM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae pbUCNP-injected mice recognize and respond to NIR light cues to elicit behavioral responses. The top two panels (C,D) show results of a light-dark box test, where mice can choose to be out in the open (in the light) or retreat into a dark box (which they naturally prefer). Control mice and those injected with pbUCNPs responded to visible light (525 nm) by retreating into the dark box, however when the light was in the NIR range (980 nm), only mice injected with pbUCNPs responded, while control mice could not discern a difference between 980 nm light and darkness. In the lower panels (E,F), mice were tested for their ‘freezing’ responses in a ‘fear conditioning’ paradigm. A 535 nm (visible) light was shown for 20s before a 2 second footshock for 6 cycles to let the mice form an associative memory (where light predicts a painful stimulus (shock)). Normal mice, after forming this memory show a ‘freezing’ or ‘immobile’ response to just the light, because they ‘remember a shock is coming’. When the researchers illuminated the mice with 535 or 980 nm light after training, control mice only froze in response to the 525 nm light, while the pbUCNP injected mice froze in response to 535 and 980 nm light! (Ma et al., 2019). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551497707075-MN0TA767RPIXUNWHD3GS/Screen+Shot+2019-03-01+at+7.34.49+PM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae Retinas from pbUCNP-injected, but not control-injected mice respond to NIR light! The first two panels above (vertical) show how a control mouse responds to visible light (top) and NIR light (no response; 2nd from top). Reciprocally, mice with pbUNCPs respond the same to both visible and non-visible NIR light. (Ma et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551404451524-84074XS40Y9KHBRWM2A8/Screen+Shot+2019-02-28+at+5.21.20+PM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551404452392-MP413V323T5XPO74XPDB/Screen+Shot+2019-02-28+at+5.35.54+PM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551496014804-TGLBVEYB2G5LDW8Z8FLS/Screen+Shot+2019-03-01+at+7.06.17+PM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae pbUNCPs allow for detection of near-infrared (NIR) light! Above, you can see the pupils of two mice, a control mouse injected with PBS, and a mouse injected with the pbUCNPs. As you can see, when exposed to no-light, both pupils are wide, indicating that they both interpret the environment as ‘dark’. However, when exposed to NIR light (980 nm), only the mouse injected with pbUCNPs shows a pupillary light reflex (PLR), indicating that they are able to discern NIR light from darkness (an ability not possessed by control mice). (Ma et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551560780289-J2HED6EJVKQXE9C2OU8L/Screen+Shot+2019-03-02+at+11.53.10+AM.png Journal Club - Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae Mice were tested on the ‘Y-shaped water maze’, where they had to swim to escape the water by finding a hidden platform located at the end of one of the arms of the maze. In these experiments, the triangle shape pointed the way to the hidden platform. Using various patterns of visible and NIR light, they demonstrated that only pbUCNP-injected mice could perform at levels significantly above chance (50%) when images were presented in NIR and visible light, indicating they could see not only the light, but discern discrete shapes as well. Note: Green in the above image represents shapes shown in visible light, while red indicates they were shown in NIR light (Ma et al., 2019). https://cancerneuro.science/new-blog/2019/1/24/rocking-promotes-sleep-in-mice-through-rhythmic-stimulation-of-the-vestibular-system monthly 0.5 2019-02-01 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1548540020400-RB1Q9T498SO7XRMI4P8J/Screen%2BShot%2B2019-01-26%2Bat%2B1.56.15%2BPM.jpg Journal Club - Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System - The Vestibular System Mediates Rocking-Induced Sleep Kompotis and colleagues demonstrate that gentle rocking promotes sleep via activation of vestibular neurons in the inner ear (Credit: Kompotis et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1548377001664-7231YRVUA2I3W9PG8GHY/figure+1+rhythmic+rocking.PNG Journal Club - Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System 1.0 Hz gentle rocking promotes NREM sleep in mice. (A) time series of sleep patterns (NREM sleep) during two baseline days without rocking (gray line), and one day of gentle rocking at different frequencies (0.25, 0.5, 1.0, and 1.5 Hz), followed by a final stationary day. Note how 1.0 and 1.5 Hz promote more NREM sleep that other frequencies. (B) comparisons of each frequency of rocking movements and how they influenced sleep. You can see that 1.5 Hz promoted the most increase in NREM sleep, but at the expense of REM sleep, therefore 1.0 Hz was deemed the ‘optimal’ frequency, as it promoted NREM sleep without disturbing REM sleep. (Credit: Kompotis et al., 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1548548247569-9C77SMK459UUVMWCE4OM/Screen+Shot+2019-01-26+at+4.10.04+PM.png Journal Club - Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1548545422540-80RX70Q4GL5GUYLUK5OO/Screen+Shot+2019-01-26+at+3.29.54+PM.png Journal Club - Rocking Promotes Sleep in Mice through Rhythmic Stimulation of the Vestibular System Rocking at 1.0 Hz promotes a shift in theta frequencies from high to low during wakefulness. (Credit: Kompotis et al., 2019) https://cancerneuro.science/new-blog/2018/12/23/my-top-5-coolest-studies-of-2018 monthly 0.5 2018-12-25 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1545768611575-O9E9G7GD30K28E070318/Screen+Shot+2018-12-25+at+3.09.51+PM.png Journal Club - My Top 5 Coolest Studies of 2018! https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1545772043491-YA3OWIA1DFQRIGTY412P/Screen+Shot+2018-12-23+at+1.29.00+PM.png Journal Club - My Top 5 Coolest Studies of 2018! Activation of the MPA—>vPAG circuit promoted hunting-like behavior in mice. Here, the researchers drew (with a little ball on a stick) the letters “B” and “G”. When the laser was off, mice were scared of the object and stayed towards the edge of the arena, but when the laser was on, they hunted the object, so closely that they essentially drew the letters with their body chasing the ball! https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1545764944395-PYN8E0ZVDIA0GS88Y2JJ/Screen+Shot+2018-12-25+at+2.08.39+PM.png Journal Club - My Top 5 Coolest Studies of 2018! Reactivation of ‘lost’ memories in mice via optogenetic stimulation of neurons that were active during memory formation in early life. (A) Stimulation of cells activated in early life 30 days later caused mice to ‘freeze’, indicating they remembered the fearful memory; (B) this effect was long lasting, up to 90 days (longest they tested) (Credit: Guskjolen et al., 2018). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1545765744318-AQQUMYQKL4TPKHXYFLJG/Screen+Shot+2018-12-25+at+2.21.55+PM.png Journal Club - My Top 5 Coolest Studies of 2018! Different populations of neurons in the BNST respond to positive (e.g., female mouse scent) or negative (e.g., predator odor) emotional stimuli . Time zero is when the stimulus was presented to the test mouse. On the Y axis you can see the fluorescent signal from CRF or CCK neurons in the BNST during stimulus presentation (credit: Giardino et al., 2018). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1545768670997-L7VMHJX2HRFFYWA8OBVP/Screen+Shot+2018-12-25+at+3.10.50+PM.png Journal Club - My Top 5 Coolest Studies of 2018! Intercellular transfer of messenger RNA via arc-encoded virus like proteins! (Credit: Pastuzyn et al., 2018) https://cancerneuro.science/new-blog/2018/11/24/defined-paraventricular-hypothalamic-populations-exhibit-differential-responses-to-food-contingent-on-caloric-state monthly 0.5 2018-12-03 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1543086658830-B3WQHTSPXNUMTLZ0J3XJ/krashes+fig+3.PNG Journal Club - Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State Fiber photometry allows for direct imaging of neural population activity in freely moving mice. In panel (A) we can see the placement of the optical fiber in the PVH to record signals coming from Glp1r-expressing neurons. Panel (B) shows that these cells do not respond to new objects placed in the environment, but do respond strongly to food when the mouse is hungry (fasted). Notably these cells don’t respond to food when the mouse is full (fed). This effect is reduced when the food is inaccessible (minutes 0-20 of panel C), but pronounced when the mice can freely access the food (minutes 20-40 of panel C). In panel (D) we can see that this effect extends to high fat diet (HFD) in addition to the mouse’s regular chow. Crh-expressing neurons showed the opposite patten (i.e., their activity was suppressed upon chow presentation after fasting; not shown) (Credit: Li et al., 2018). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1543201132332-DIQAKYKVNQGVVGM5OLPR/Screen+Shot+2018-11-25+at+6.57.30+PM.png Journal Club - Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State The paraventricular hypothalamus (PVH; pictured above) contains many different unique cell types. The above image shows little overlap between two primary cell types in this region, those expressing melanocortin-4 receptor (Mc4r) and oxytocin (Oxt) (2.1% overlap). (Credit: Li et al., 2018) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1543201567745-AFW4MC44D2C19EJI0BUW/Screen+Shot+2018-11-25+at+7.05.44+PM.png Journal Club - Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State Induction of cFos in genetically-defined neuronal subtypes within the PVH after fasting or fasting followed by a 2-hour re-feeding session. As you can see, nearly all subtypes showed changes in activity (except Oxt neurons) with these manipulations. Some increased activity (Glp1r and Mc4r) while Crh neurons decreased their activity upon re-feeding. (cFos in RED with cell types in GREEN). (Credit: Li et al., 2018) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1543203350897-70E6S8B5VSTW09E8O6L9/Screen+Shot+2018-11-25+at+7.35.16+PM.png Journal Club - Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State https://cancerneuro.science/new-blog/2018/11/8/sfn2018-day-4-brains-reward-system-dictates-sleep-and-wakefulness monthly 0.5 2018-11-08 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541698953748-EIW6HMM7O6WJOEK8EOF9/vta+da+wakefulness+ada.png Journal Club - #SFN2018 Day 4: Brain's Reward System Dictates Sleep and Wakefulness Activation of VTA-dopamine neurons (TH-positive) strongly promotes wakefulness. You can see that when these neurons are stimulated (by light sensitive ChR2 activation), the mice rapidly wake up (panels c,d,e)(Credit: Eban-Rothschild et al., 2016; Nature Neuroscience) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541699001219-M32QUJ15CMVIK1O62OBT/photometry+example.png Journal Club - #SFN2018 Day 4: Brain's Reward System Dictates Sleep and Wakefulness Example of a fiber photometry trace showing the activity of GABA neurons across sleep-wake states. As you can see, these neurons are mostly active during wakefulness and REM sleep compared to NREM sleep (wake = white background, NREM = blue, REM = red) (Credit: Jeremy C Borniger, PhD, Stanford University) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541698883930-T5K0OL0HF1SOHEU8X70Z/vgat+and+da+vta.jpeg Journal Club - #SFN2018 Day 4: Brain's Reward System Dictates Sleep and Wakefulness Dopamine (green) and GABA (red) expressing neurons in the mouse ventral tegmental area (VTA; outlined) studies by Xiao Yu and colleagues demonstrates that these neurons bidirectionally regulate sleep and wakefulness (Credit: Jeremy C Borniger, PhD; Stanford University) https://cancerneuro.science/new-blog/2018/11/6/sfn2018-day-3-chili-peppers-inflammatory-painand-i-won-an-award- monthly 0.5 2018-11-06 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541530941599-QFHAPV97R0ETVKK5NPMM/trpv1+and+trka.png Journal Club - #SFN2018 Day 3: Chili Peppers, Inflammatory Pain...and I Won an Award! :) Neurons projecting to the inflamed knee (‘knee neurons’ labeled with FB) from the dorsal root ganglion expressed a much higher amount of the capsaicin receptor (TRPV1), without changes in the receptor for Nerve Growth Factor (a molecule associated with increased neural sensitivity; TrkA) (Credit: Chakrabarti et al., 2018; Neuropharmacology) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541530854691-EBWQN2D3RQ2O5G1WI4EB/DRG+.png Journal Club - #SFN2018 Day 3: Chili Peppers, Inflammatory Pain...and I Won an Award! :) The dorsal root ganglia (there’s two at almost all vertebrae) relay sensory information arriving from everywhere in the body. They serve a key role in reflex responses (e.g., to a hot grill) that occur before the brain becomes “aware” that something happened, and they also act as a highway to transmit information to the spinal cord and up to the brain (Credit: Quora.com) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541531031145-KKJ6Z9Z2OH22V5H15UDL/Burrows.png Journal Club - #SFN2018 Day 3: Chili Peppers, Inflammatory Pain...and I Won an Award! :) Blocking TRPV1 signaling using a receptor antagonist prevents inflammatory joint pain elicited by injections of CFA. In panels B and C you can see that without the antagonist, the mice fail to show their normal happy digging behaviors. However, with the antagonist, their behavior returns to normal, indicating that they are no longer in pain (Credit: Chakrabarti et al., 2018; Neuropharmacology) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541531500502-V27NVZDRQBFOL5202VUA/Me+and+Rae.jpg Journal Club - #SFN2018 Day 3: Chili Peppers, Inflammatory Pain...and I Won an Award! :) Me (left) and SBN President Rae Silver, a legend in the field for her work on circadian rhythms, awarding me the WC Young Recent Graduate Award at the SBN Social event in the Marriott Marquis next to the San Diego Convention Center. https://cancerneuro.science/new-blog/2018/11/5/sfn18-day-2-recap-controlling-neurons-with-ultrasound-and-a-novel-avenue-for-depression-treatment monthly 0.5 2018-11-05 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541423901806-NBT3WKUKKI8CLEQY35L5/AgRP+neurons+Gcamp.png Journal Club - #SFN18 Day 2 Recap: Controlling Neurons with Ultrasound and a Novel Avenue for Depression Treatment? AgRP neurons in the arcuate nucleus expressing the calcium indicator GCaMP6. These cells are powerful regulators of feeding behavior and metabolism (Credit: Srisai et al., 2017; Nature Communications) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541424096142-USVF21C3GDIDRIR34IY1/agrp+and+pomc+anatomy.png Journal Club - #SFN18 Day 2 Recap: Controlling Neurons with Ultrasound and a Novel Avenue for Depression Treatment? Viral injections into the arcuate nucleus of POMC-Cre mice (left panels; projections in red) shows their wide axonal distribution throughout the brain. Similarly, injections into the arcuate nucleus of AgRP-cre mice demonstrate that they also project throughout the brain, although in a different pattern (right panels, projections in green) (Credit: Wang et al., 2015; Frontiers in Neuroanatomy) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541424041048-TJQ6WG71CTB8CDE26HKE/AgRP+and+POMC+arcuate.png Journal Club - #SFN18 Day 2 Recap: Controlling Neurons with Ultrasound and a Novel Avenue for Depression Treatment? AgRP neurons in the arcuate promote food intake while POMC neurons inhibit food intake via their actions on downstream MC4R- expressing neurons in the paraventricular nucleus (Credit: Carol A. Rouzer, Vanderbilt University) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541424631166-UDWG6XC6MT15ZI7PAC79/sonogenetics+2015.png Journal Club - #SFN18 Day 2 Recap: Controlling Neurons with Ultrasound and a Novel Avenue for Depression Treatment? Sonogenetics allows for non-invasive control of neural activity. Here, in C. elegans with PVD neurons expressing the ultrasound-sensitive protein (TRP-4) and the calcium indicator GCaMP3, we can see that ultrasound exposure drastically increases calcium activity in these neurons, indicating ultrasound mediated neural activation. Warmer colors indicate more GCaMP3 fluorescence = more activity (Credit: Ibsen et al., 2015; Nature Communications) https://cancerneuro.science/new-blog/2018/11/3/sfn18-day-1-recap-circadian-surprises-and-fancy-new-tech monthly 0.5 2018-11-08 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541357866414-6JSDYPDOJAHW90GGIMPV/Fly+WAKE+abstract.png Journal Club - #SFN18 Day 1 Recap: Circadian Surprises and Blowing Up Brains! WAKE regulates sleep quality through appropriate timing of neural firing codes (Credit: Tabuchi et al., 2018; Cell) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541358045679-03PSL1D6FHB5JWOBPYJP/Expansion+microscopy.png Journal Club - #SFN18 Day 1 Recap: Circadian Surprises and Blowing Up Brains! Expansion microscopy allows for uniform expansion of a biological sample. Here, we see a brain slice (in panel B) which has been weaved into a polymer mesh with biomolecular anchors. When the polymer is expanded (‘Just add water’), it pulls the biomolecules along with it, maintaining the relative spacing between structures. In (C ) we can see that same brain slice ‘expanded’, revealing tiny pieces of biology previously too small to see(Credit: Chen et al., 2015; Science). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541358110835-J4363N06HEOAAEW5HLPN/Iterative+Expansion.png Journal Club - #SFN18 Day 1 Recap: Circadian Surprises and Blowing Up Brains! Iterative Expansion Microscopy allows for sample expansion up to 20x! Panel A shows dendritic spines without expansion, panel B shows the same at 4.5x expansion, and panel C shows dendritic spines at 20x expansion after the iterative process is complete (Credit: Chang et al., 2017; Nature Methods) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541357761725-F657C8H1TYE6LI3HR511/SCN+merge.png Journal Club - #SFN18 Day 1 Recap: Circadian Surprises and Blowing Up Brains! The suprachiasmatic nuclei (pictured above) serve as the master clocks controlling mammalian circadian rhythms (Credit: Jeremy C. Borniger, PhD; Stanford) https://cancerneuro.science/new-blog/2018/10/22/my-coverage-of-sfn2018-nov-3-7th monthly 0.5 2018-10-26 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1540250491478-D5MNN18DN5WW17UI9LDO/sfn+2018.png Journal Club - My Coverage of #SfN2018 (Nov. 3-7th) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1540250760206-G2BVQA5BUYBJ2L6068T2/JCB+SFN+2015.jpg Journal Club - My Coverage of #SfN2018 (Nov. 3-7th) Me in what is possibly the wrinkliest shirt in existence at #SFN 2015. https://cancerneuro.science/new-blog/2018/9/30/tcellnarcolepsy monthly 0.5 2018-10-02 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1538418214263-0QXKL4ULLVYICF81Z20S/Screen+Shot+2018-10-01+at+11.22.56+AM.png Journal Club - T cells in patients with narcolepsy target self-antigens of hypocretin neurons Hypocretin (green) neurons in the mouse lateral hypothalamus co-stained with anti-cFos (red). Latorre et al., 2018 demonstrate that autoreactive CD4+ T-cells in patients with narcolepsy specifically target epitopes present on these neurons, leading to their destruction (Credit: JCB). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1538324153097-C1ZQDK2DI1Z84MWTS0R5/hcrt+specific+clones.PNG Journal Club - T cells in patients with narcolepsy target self-antigens of hypocretin neurons Specific CD4+ autoreactive T-cell clones targeting hypocretin peptides in patients with narcolepsy (Latorre et al., 2018). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1538444708252-F11FR6UQ2A6K1UJFL5HF/epitope+mapping+of+T+cell+clones.PNG Journal Club - T cells in patients with narcolepsy target self-antigens of hypocretin neurons Epitope mapping of hcrt and TRIB2-specific autoreactive T cells. Each patient sample contains T-cell populations that react to different regions along the hypocretin and TRIB2 amino acid sequences. This is driven by antigen presentation through HLA-DR/DQ/DP, as blockade of these interactions prevent T cell expansion upon stimulation (Latorre et al., 2018). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1538443778069-VCHUBDZBBH8KKF76FKSK/t+cell+library+method.PNG Journal Club - T cells in patients with narcolepsy target self-antigens of hypocretin neurons Hcrt-specific autoreactive T cells detected using the T cell library method. Each dot represents a single T cell, with proliferation measured in response to peptide stimulation reported in counts per minute (c.p.m) after incubation with [3H]-thymidine to label proliferating cells. ‘Positive’ T cell responses were considered > 2,000 c.p.m as the background (unstimulated) proliferation rate was ~1,500 c.p.m. Note the strong proliferative response of T cells to hcrt peptide fragments in narcoleptics (P#) versus controls (C#). (NT1 = narcolepsy type 1, NT2 = narcolepsy type 2) (Latorre et al., 2018). https://cancerneuro.science/new-blog/2018/9/16/september-2018-1 monthly 0.5 2018-09-23 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1537140956999-KH168FXTHEQ7JW9WS954/Screen+Shot+2018-09-16+at+4.35.27+PM.png Journal Club - Modulation of anti-tumor immunity by the brain's reward system Figure 4: ‘VTA-activated’ myeloid derived suppressor cells (MDSCs) are necessary and sufficient to suppress tumor growth. Adoptive transfer of ‘activated’ MDSCs suppressed tumor growth in mice that had not been ‘VTA-activated’. https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1537131278748-TT1FZPXJ9PI02PZWFQ8E/fig+1.PNG Journal Club - Modulation of anti-tumor immunity by the brain's reward system Figure 1: Using DREADDs to selectively manipulate VTA-Dopamine neurons in the context of cancer. https://cancerneuro.science/new-blog/tag/VTA monthly 0.5 https://cancerneuro.science/new-blog/tag/DREADDs monthly 0.5 https://cancerneuro.science/new-blog/tag/cancer monthly 0.5 https://cancerneuro.science/new-blog/tag/Immunity monthly 0.5 https://cancerneuro.science/news daily 0.75 2024-09-17 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535325722762-GAXWFDPZEHFFQ1ZHE8FI/Screen+Shot+2018-08-26+at+4.21.35+PM.png Lab News https://cancerneuro.science/news/2024/9/17/new-lab-members-and-biorxiv-preprint monthly 0.5 2024-09-17 https://cancerneuro.science/news/2022/12/2/the-lab-presents-4-posters-at-sfn2022 monthly 0.5 2022-12-02 https://cancerneuro.science/news/2022/7/13/review-published-in-advanced-biology monthly 0.5 2022-07-13 https://cancerneuro.science/news/2022/5/19/berisha-amp-shutkind-review-published-in-frontiers-in-neuroscience monthly 0.5 2022-05-19 https://cancerneuro.science/news/2022/5/19/prostate-cancer-grant-funded monthly 0.5 2022-05-19 https://cancerneuro.science/news/2021/12/2/starr-consortium-grant-funded monthly 0.5 2021-12-02 https://cancerneuro.science/news/2021/10/26/dod-discovery-grant-funded monthly 0.5 2021-10-26 https://cancerneuro.science/news/2021/9/24/labs-first-review-paper-out-now-in-trends-in-neuroscience monthly 0.5 2021-09-24 https://cancerneuro.science/news/2021/2/25/new-paper-published monthly 0.5 2021-02-25 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1614289622091-OLJVZZY5N4D4XGJ395LZ/Figure+1.png Lab News - New paper published! https://cancerneuro.science/news/2021/1/28/new-paper-online monthly 0.5 2021-01-28 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1611857512462-LXLR3CFAWLHIWOHLH2SX/otero+paper+fig.PNG Lab News - New paper online! https://cancerneuro.science/news/2020/11/23/aacr-nextgen-grant-funded monthly 0.5 2020-11-23 https://cancerneuro.science/news/2020/9/11/paper-published-in-science-advances monthly 0.5 2020-09-11 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1599832362265-HT4XQXCRVAY658VKMFQH/FIgure+6.PNG Lab News - Paper published in Science Advances! https://cancerneuro.science/news/2020/8/27/first-postdoc-joins-the-lab-nikita-francis monthly 0.5 2020-08-28 https://cancerneuro.science/news/2020/6/1/commentary-published-in-cell monthly 0.5 2020-06-01 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1591046247379-17ESDC7LSE2YV3K5FC2P/cancer+neuro.jpg Lab News - Commentary published in Cell https://cancerneuro.science/news/2020/6/1/preprint-published-on-biorxiv monthly 0.5 2020-06-01 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1591045216350-EG5XXKKP9PK2SXQ7TJQO/Screen+Shot+2020-06-01+at+5.00.02+PM.png Lab News - Preprint published on BioRxiv https://cancerneuro.science/news/2020/1/18/chapter-published monthly 0.5 2020-01-18 https://cancerneuro.science/news/2019/9/19/new-preprint-available-on-biorxiv monthly 0.5 2019-09-19 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1568915984112-CA9ZNACFJWCLFWYM4SRQ/EE15bbEVUAEu6_Z.jpeg Lab News - New Preprint available on BioRxiv! https://cancerneuro.science/news/2019/9/9/paper-published-in-neurobiology-of-aging monthly 0.5 2019-09-10 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1568076196342-4ZWCEOCPL593JSO5RIKM/Screen+Shot+2019-09-09+at+5.42.50+PM.png Lab News - Paper published in Neurobiology of Aging! Estradiol enhances biological rhythms in aged female rats. https://cancerneuro.science/news/2019/9/4/jeremy-awarded-narsad-young-investigator-grant-from-bbrf monthly 0.5 2019-09-04 https://cancerneuro.science/news/2019/9/3/answers-featured-at-science-careers monthly 0.5 2019-09-03 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1567552170389-G6FLS5OAYCD9CB9UBLWZ/IMG_2480.png Lab News - Answers Featured at Science Careers A snippet of one of my lab notebooks (Credit: JCB). https://cancerneuro.science/news/2019/6/29/k99r00-application-receives-best-possible-impact-score monthly 0.5 2019-06-30 https://cancerneuro.science/news/2019/6/27/awarded-the-american-college-of-neuropsychopharmacology-acnp-travel-award monthly 0.5 2019-06-27 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1561663979171-G3AGI3EJZ9FKLA4AUQ80/e6b4a90bade979c251b39d8d500ad46b.jpeg Lab News - Awarded the American College of Neuropsychopharmacology (ACNP) Travel Award! https://cancerneuro.science/news/2019/6/27/presented-at-the-society-for-behavioral-neuroendocrinology-annual-meeting monthly 0.5 2019-06-27 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1561663761343-STTKBDTG07N9C2CI6SZ3/SBN+talk.jpg Lab News - Presented at the Society for Behavioral Neuroendocrinology Annual Meeting https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1561663738948-6DT01Z7G7ROPCNCP8N5S/IMG_20190621_083152+copy.jpg Lab News - Presented at the Society for Behavioral Neuroendocrinology Annual Meeting https://cancerneuro.science/news/2019/5/29/paper-published-in-molecular-psychiatry monthly 0.5 2019-05-30 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1559178991337-AHGUQQR6VURZKSOSE9TW/Picture1.png Lab News - Paper published in Molecular Psychiatry! Our paper demonstrates that low levels of light at night influence the expression of vascular endothelial growth factor (VEGF) and its receptors, along with cytokine mRNA, in the murine hippocampus. Pictured above is DyLight-594 labeled tomato lectin (red), which labels all active capillaries in the brain (Credit: JCB) https://cancerneuro.science/news/2019/5/7/new-review-paper-available-online-as-a-preprint monthly 0.5 2019-05-07 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1557266002264-DY9C3S1X0Y2DJPLD7D0Y/figureone.jpg Lab News - New review paper available online as a preprint https://cancerneuro.science/news/2019/4/29/paper-accepted-in-molecular-psychiatry- monthly 0.5 2019-04-29 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1556563550075-4MYE4OYVGOPCSIEAURMG/Screen+Shot+2019-04-29+at+11.45.36+AM.png Lab News - Paper accepted in Molecular Psychiatry ! Acute changes in locomotor behavior in response to light at night. https://cancerneuro.science/news/2019/4/20/accepted-job-offer-at-cold-spring-harbor-laboratory monthly 0.5 2019-04-20 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1555784992863-KOXCOSR6IPHQW2PUSQ31/homepageimage1.jpg Lab News - Accepted Job Offer at Cold Spring Harbor Laboratory! https://cancerneuro.science/news/2019/3/27/recognized-as-a-finalist-in-the-ibiology-young-scientist-seminar-series monthly 0.5 2019-03-27 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1553704500512-D873IYIZQEQ8IV2YMZH0/Screen+Shot+2019-03-27+at+9.34.46+AM.png Lab News - Recognized as a finalist in the iBiology Young Scientist Seminar Series https://cancerneuro.science/news/2019/3/23/review-paper-published-in-the-journal-of-cancer-metastasis-and-treatment monthly 0.5 2019-03-24 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1553389025794-08XIVEBVBBFNNR3Z57TC/Screen+Shot+2019-03-23+at+5.56.45+PM.png Lab News - Review paper published in the Journal of Cancer Metastasis and Treatment Examples of neural circuits that play an important role in cancer-associated systemic disruption (e.g., circadian rhythm and sleep abnormalities, systemic inflammation, and anorexia/cachexia). https://cancerneuro.science/news/2019/2/27/chapter-published-in-oxford-university-press monthly 0.5 2019-02-27 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1551305226021-MMIDRRCAT6OL97WRWOU4/hypocretinarousalnetwork.png Lab News - Chapter published in Oxford University Press Hypocretin neurons act as integrators of exogenous and endogenous signals. https://cancerneuro.science/news/2019/2/19/k99r00-nominated-by-stanford-cancer-institute monthly 0.5 2019-02-19 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1550604576712-JK5VG9V969FXUSCYVFI0/Screen+Shot+2019-02-19+at+11.29.05+AM.png Lab News - K99/R00 Nominated by Stanford Cancer Institute https://cancerneuro.science/news/2019/1/28/paper-accepted-at-the-journal-of-physiology monthly 0.5 2019-03-20 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1548696591361-SFZEGV3WESVOD21NTD8S/Screen+Shot+2019-01-28+at+9.29.32+AM.png Lab News - Paper accepted at the Journal of Physiology! PHOX2B-derived brainstem astrocytes contribute to chemosensory control of breathing and sleep homeostasis. https://cancerneuro.science/news/2018/12/15/received-innovator-grant monthly 0.5 2019-04-05 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1544904144987-FYXAVDA8WABPT3NMUUCB/Picture1.png Lab News - Received Innovator Grant! Experimental workflow for examining brain-immune interactions using DBS and mass cytometry (Credit: JCB). https://cancerneuro.science/news/2018/10/31/received-wc-young-recent-graduate-award monthly 0.5 2018-10-31 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1541011701855-YZ8GAV8HFO1KIPQ2Y5LI/sbn.jpeg Lab News - Received WC Young Recent Graduate Award! https://cancerneuro.science/news/2018/10/8/invited-to-talk-at-cold-spring-harbor-labs monthly 0.5 2018-10-08 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1539037832949-31L7T12D4NBPVDWU3O8I/Hero-images_Home_Campus-04.jpg Lab News - Invited to talk at Cold Spring Harbor Labs Cold Spring Harbor Lab’s Campus (Credit: CSHL) https://cancerneuro.science/news/2018/9/27/selection-as-an-official-sfn2018-meeting-blogger monthly 0.5 2018-09-27 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1538087216868-54YSFXJ8K5ODZ6Y326QM/NS18-navigation+image_FINAL.jpg Lab News - Selection as an official #SfN2018 meeting blogger https://cancerneuro.science/news/2018/9/3/nih-brain-initiative-f32-is-funded monthly 0.5 2018-09-13 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1536858395184-8KXOUBBSS7NE8D1EDLD3/grant+image.PNG Lab News - NIH BRAIN Initiative F32 is funded! Schematic sagittal section showing hypocretin projections to arousal centers (LC/VTA). These downstream regions innervate areas important for learning and memory (i.e., hippocampus, mPFC…) (credit: JCB). https://cancerneuro.science/news/2018/8/26/media-coverage-for-cell-metabolism-paper monthly 0.5 2018-09-13 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1536858054312-K6EBU6D5SV4DYD3P1194/tumor+systemic+disruption.PNG Lab News - Select Media Coverage of our Cell Metabolism Paper Tumor cells can cause quite a systemic mess. (Image Credit: Lara Crow; Macmillan publishers limited). https://cancerneuro.science/journal-club-archives daily 0.75 2019-12-31 https://cancerneuro.science/workshops daily 0.75 2020-04-06 https://cancerneuro.science/workshops/2014/9/15/yoga-aerobics-j7h7z monthly 0.5 2019-04-10 https://cancerneuro.science/workshops/2014/9/15/yoga-for-toddlers-hybaw monthly 0.5 2019-04-10 https://cancerneuro.science/workshops/2014/11/1/instructor-training-pe9wf monthly 0.5 2019-04-10 https://cancerneuro.science/resources daily 0.75 2021-08-19 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535679123759-TC20Q95LZJPK687VOEAJ/382556_3540971718294_2122940711_n.jpg Resources https://cancerneuro.science/publications daily 0.75 2022-05-19 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535677642457-5263LA4IO8K1PGLLJAAA/Screen+Shot+2018-08-30+at+6.06.39+PM.png Publications https://cancerneuro.science/outreach daily 0.75 2020-06-10 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535737371676-3AE64GK2B8LFEW7Z184P/Screen+Shot+2018-08-31+at+10.42.28+AM.png Outreach - Photoperiod and brain blood flow: Changing day length to alter cerebral perfusion This is a summary of our research on how day length (photoperiod) alters blood flow to the brain in white-footed mice (click link above; image: JCB). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535739773029-SRCJ9VYGW86S2PDVFP1Z/Screen+Shot+2018-08-31+at+11.22.31+AM.png Outreach - Snark-hunters once more: Rejuvenating the comparative approach in modern neuroscience I wrote this to highlight the myopic approaches of modern neuroscience, and emphasize that we need to take advantage of more of the available nervous systems on the planet (click link above; image: Frank Beach, 1950). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535737880712-HALB8ET45WRWJ7L3OQQM/Screen+Shot+2018-08-31+at+10.50.53+AM.png Outreach - Melatonin: An old hormone with new tricks This describes some exciting findings relating melatonin with relapse rates in multiple sclerosis. (click link above.; image: Jooyeun Lee) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535736832036-J2R08B9F9DEELPHZFHXF/Screen+Shot+2018-08-31+at+10.33.33+AM.png Outreach - Do cigarettes have long lasting effects on children's sleep? This is a summary I wrote for Frontiers for Young Minds, detailing how early life exposure to nicotine alters sleep in adulthood (click link above; image: Frontiers for Young Minds). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535738099065-F8VBIBBHJAZ32NKN6MQN/Screen+Shot+2018-08-31+at+10.54.40+AM.png Outreach - Messing with the ‘Flip-Flop’ Switch: Why Getting Sick Makes You Sleepy This is a piece describing why we so often feel tired and low energy during periods of sickness (click link above; image: Jooyeun Lee) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535738476270-ASN3QF9LJ7YVO45YTY05/Screen+Shot+2018-08-31+at+11.00.57+AM.png Outreach - Leaping into the unknown I wrote a piece for Science about switching career paths from anthropology to neuroscience, and the hardships that came with that. (click link above; image: Robert Neubecker). https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1536202180278-WE9Q0109QYP3APVW0QHS/Screen+Shot+2018-09-05+at+7.48.55+PM.png Outreach https://cancerneuro.science/home daily 1.0 2025-04-22 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1553123419224-S8T2Z6R79YYPTR5WR8NV/Watson+%26+Preedy+Figure+1.png Home Cancer causes systemic disruption. Through nervous, endocrine, metabolic, and immune (NEMI) pathways, the brain senses changes in the periphery caused by tumors. The brain responds through these systems and powerfully through the autonomic nervous system. This cross-talk results in many symptoms associated with cancer, and influence how the tumor grows and metastasizes. My work aims to understand how the brain and cancer talk to each other, leading to changes in sleep, behavior, resistance to treatment, and tumor progression. (Credit: Borniger & Nevarez, 2019) https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1536023898119-DHCCPMBX11Q4OA3HW7QG/banner2.png Home https://cancerneuro.science/what-we-do daily 0.75 2021-09-24 https://images.squarespace-cdn.com/content/v1/5b82081250a54f02ee0758c8/1535421705253-EI8HYTD9R9IK2OYO7V2G/graphical+abstract Research Tumors alter leptin/ghrelin signaling, which results in aberrant activation of hypothalamic hypocretin/orexin neurons. This promotes poor sleep, and changes in glucose metabolism via the sympathetic nervous system. 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