WHAT’S NEW WITH OUR STUDENTS?
Awards and Fellowships:
Congratulations to Bryan Barker, who was awarded an American Epilepsy Society’s Predoctoral Fellowship:
A neuroscience Ph.D candidate in Manoj Patel’s lab has received the American Epilepsy Society’s Predoctoral Fellowship for his dissertation work in the field of epilepsy “The role of T-type calcium channels in neuronal hyperexcitability in the subiculum in temporal lobe epilepsy.” Temporal lobe epilepsy (TLE) is a debilitating neurological disorder that is characterized by recurrent spontaneous seizures that originate in the temporal lobe of the brain. There is no cure for TLE; seizures can only be suppressed using anticonvulsant drugs. Despite a plethora of treatment options, 30% of TLE patients do not respond to any currently available therapies. To improve treatment efficacy it is essential to develop a better understanding of the alterations in neuronal physiology that occur during the development of epilepsy and how these changes ultimately culminate in the occurrence of spontaneous seizures. My dissertation research focuses on the understudied subiculum, a brain region that acts as the output of the hippocampus. Specifically, my goal is to understand how alterations in T-type calcium channel activity in TLE, lead to the increase in neuronal activity associated with seizure initiation.
Congratulations to Alex Keller, who was awarded an American Heart Association Predoctoral Fellowship:
Alex Keller, a Pharmacology Ph.D. candidate in Brant Isakson’s laboratory has received a pre-doctoral fellowship from the American Heart Association to research “Mechanisms of ATP release from Pannexin 1 in Red Blood Cells in response to hypoxia.” Regulation of blood flow to supply oxygen at an appropriate rate to meet the metabolic demand of tissues across the body is an imperative homeostatic process. Red blood cells have been shown to release ATP in response to hypoxic conditions, resulting in arteriolar dilation in a manner that could contribute to increased perfusion of hypoxic tissues. However, the details of the ATP release mechanism from red blood cells in this context are unclear. Pannexin 1, a channel believed to be involved in this ATP release pathway, is of particular interest to the Isakson lab. By studying the activation of Pannexin 1 in this context, Alex seeks to elucidate the molecular pathway underlying ATP release from red blood cells in response to hypoxia. In addition, he plans to use modern techniques to study the broader pathway in more physiologically relevant contexts than those in which it has previously been examined. Overall, this research will improve our understanding of an important mode of blood flow regulation while simultaneously offering an opportunity to learn more about under-studied red blood cell signaling mechanisms.
Congratulations to Steven Keller, who was awarded an American Heart Association Predoctoral Fellowship:
A Molecular Physiology and Biological Physics graduate student co-mentored by Linda Columbus and Brant Isakson has received an American Heart Association Pre-Doctoral Fellowship. “Increasing nitric oxide (NO) via an alpha globin mimetic peptide as a treatment for sickle cell-induced pulmonary hypertension.” Endogenously produced NO is one of the most potent mechanisms to maintain blood pressure homeostasis. A recently discovered regulator of NO production in vascular endothelium is the direct interaction of endothelial nitric oxide synthase (eNOS) and the alpha chain of hemoglobin, putting a sink for NO in complex with its source. We are using a peptide mimicking the binding sequence of alpha globin to disrupt alpha globin/eNOS complex formation and increase NO availability, thus lowering blood pressure. Structural aspects of this interaction are being investigated in the context of hypertensive pathologies, especially pulmonary hypertension, a common condition in sickle cell disease that is associated with high mortality.
Congratulations to Aldo Nascimento, who was awarded a National Cancer Institute NRSA Predoctoral Fellowship:
Mitochondria are highly dynamic, and the fusion and fission of mitochondria represent an increasingly important, but poorly understood node of cellular regulation. Recent studies have shown that defects in the fusion-fission balance have detrimental effects on human health including an involvement in diabetes and cancer. Further, many of the processes regulated by mitochondrial dynamics overlap with those that are induced by oncogenic Ras signaling. We have recently published data which demonstrates that activated Ras can signal through the MAPK pathway to promote mitochondrial fission. This mitochondrial fission in turn is important for MAPK-driven tumor growth. What remains to be understood is why the mitochondrial fission is important for tumor growth. Thus, we now shift our focus to determine which physiological processes necessary for tumor growth are regulated by an increase in mitochondrial fission. If successful, these studies will reveal a novel, physiologically relevant mechanistic insights of how Ras-induced mitochondrial fission promotes tumor growth. Furthermore, these studies will elucidate novel regulatory mechanisms of mitochondrial dynamics and potentially provide novel therapeutic targets for the treatment of Ras-driven cancers.
Congratulations to Tori Osinski, who was awarded an American Heart Association Predoctoral Fellowship:
A Pathology Ph.D. candidate in the lab or Coleen McNamara has received an American Heart Association Predoctoral Fellowship. “Assessing regulation of adipose tissue angiogenesis by Id3 and MCP-1-expressing adipocyte progenitor cells.” Adipose tissue (fat) expansion involves two important processes: adipogenesis, the formation of new adipocytes (fat cells), and angiogenesis, the formation of new microvascular blood vessels. Defects in either can prevent proper growth of fat tissue during both normal development as well as pathological states such as obesity. Our lab has recently demonstrated a role for the transcription factor Inhibitor of differentiation 3 (Id3) in both of these processes. Id3 regulates the proliferation of adipocyte progenitor cells, which express high levels of Monocyte Chemoattractant Protein-1 (MCP-1). MCP-1 is a secreted molecule that influences monocyte and macrophage movement within tissues and macrophages play important roles in regulating inflammation and angiogenesis. I seek to identify the specific molecular and cellular roles of Id3, adipocyte progenitor cells, and macrophages in angiogenesis during adipose tissue expansion. The overall goal of this study is to better understand what goes on in adipose tissue during metabolic disorders such as obesity.
Congratulations: 2016 Wagner Fellowship Awardees
We are thrilled to announce that the Wagner Fellowship fund was able to support 12 BIMS students this year due to the incredible generosity of Dr. Robert Wagner and his wife Mary. Dr. Wagner served as Professor and Chair of Microbiology from 1967-1994 and contributed in so many ways to the School of Medicine, UVA, and the scientific community at large. These fellowships are a lasting tribute to his dedication to student training, his encouragement of young scientists, and his love of UVA. Please join us in congratulating the 2016 Wagner Fellows.
Rising 3rd year students:
Rising 4th/5th year students:
Congratulations to the 2016 winner of the Peach Award:
Jim received his PhD in neuroscience in May of 2016. He trained in the laboratory of Dr. Jony Kipnis, where he made seminal discoveries regarding the role of microglia in neurodevelopmental diseases. His research has been published in Immunity, Journal of Immunology, and Nature. He has also published review articles in Neurobiology of Disease, F1000Prime Reports, and Trends in Immunology. He was the recipient of an NRSA predoctoral (MD/PhD) fellowship from the National Institute of Allergy and Infectious Diseases at the NIH. He is now completing the third year of his MD training as part of the combined MD/PhD Medical Scientist Training Program at the University of Virginia.
Congratulations to the 2016 winner of the Hungerford Prize:
From left to right: Jim Casanova (mentor), Nancy Hungerford, Charles Hungerford, Emily Billings (sitting)
Emily received her PhD in microbiology in May of 2016. She trained in the laboratory of Dr. Jim Casanova, where she discovered a new mechanism through which bacteria are recognized and cleared by macrophages. Her research is published in Science Signaling and Current Biology. In addition to her research, Emily was extremely active in the Graduate Biosciences Society (GBS), serving as Academic Chair and then President of GBS during her PhD training. Emily received the Graduate Biosciences Student Leadership Award in 2015 in recognition of her notable academic, professional, and service contributions to the University of Virginia and BIMS graduate program. She is currently working as a Senior Analyst at Gryphon Scientific, LLC based in Takoma Park, MD.
Recent Publications of Our Students
Z. Chitforoushzadeh, Z. Ye, Z. Sheng, S. LaRue, R.C. Fry, D.A. Lauffenburger, and K.A. Janes. TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data sensors. 2016. Science Signaling 9:ra59. (http://stke.sciencemag.org/content/9/431/ra59.full)
S.E. Adamson, R. Griffiths, R. Moravec, R., S. Senthivinayagam, G. Montgomery, W. Chen, J. Han, P.R. Sharma, G.R. Mullins, S.A. Gorski, J.A. Cooper, A. Kadl, K. Enfield, T.J. Braciale, T.E. Harris, N. Leitinger. 2016. Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation. Journal of Clinical Investigation 126:1311-1322. (https://www.jci.org/articles/view/79590)
O.A. Cherepanova, D. Gomez, L.S. Shankman, P. Swiatlowska, J. Williams, O.F. Sarmento, G.F. Alencar, D.L. Hess, M.H. Bevard, E.S. Greene, M. Murgai, S.D. Turner, Y.J. Geng, S. Bekiranov, J.J. Connelly, A. Tomlin, G.K. Owens. 2016. Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. Nature Medicine 22:657-665. (http://www.nature.com/nm/journal/v22/n6/full/nm.4109.html)
J. Harakal, C. Rival, H. Qiao and K.S. Tung. 2016. Regulatory T cells control Th2-dominant murine autoimmune gastritis. Journal of Immunology 197:27-41. (http://www.jimmunol.org/content/197/1/27.long)
V.K. Mony*, S. Benjamin*, E. J. O’Rourke. 2016. A lysosome-centered view of nutrient homeostasis. Autophagy 12:619-631. (*co-first authors) (http://www.tandfonline.com/doi/full/10.1080/15548627.2016.1147671?scroll=top&needAccess=true)
L.M. Muehling, D.T. Mai, W.W. Kwok, P.W. Heymann, A. Pomés and J.A. Woodfolk. 2016. Circulating memory CD4+ T cells target conserved eptiopes of Rhinovirus capsid proteins and respond rapidly to experimental infection in humans. Journal of Immunology Sep 2. pii: 1600663. [Epub ahead of print] PubMed PMID: 27591323.
C.Z. Han, I.J. Juncadella, J.M. Kinchen, M.W. Buckley, A.L. Klibanov, K. Dryden, S. Onengut-Gumuscu, U. Erdbrügger, Y.M. Shim, K.S. Tung, and K.S. Ravichandran. 2016. Macrophages redirect phagocytosis by non-professional phagocytes and influence inflammation. Nature. November 7. doi 10.1038/nature20141
- Highlighted via a “Dispatch” in Current Biology, written by Dr. Sergio Grinstein
- Highlighted in Nature Reviews Immunology as a feature paper
C.S. Lee, K.K. Penberthy, K.M. Wheeler, I.J. Jucadella, P. Vandenabeele, J.J. Lysiak., K.S. Ravichadran. 2016. Boosting cell clearance in vivo attenuates inflammatory colitis. Immunity 44:807-820.
A.J. Filiano, Y. Xu, N.J. Tustison, R.L. Marsh, W. Baker, I Smirnov, C.C. Overal, S.P. Gadani, S.D. Turner, Z. Weng, S.N. Peerzade, H. Chen, K.S. Lee, M.M. Scott, M.P. Beenhakker, V. Litvak and J. Kipnis. 2016. Uniexpected role of interferon-Υ in regulating neuronal connectivity and social behavior. Nature 535:425-429. http://www.nature.com/nature/journal/v535/n7612/full/nature18626.html
S.P. Gadani and J. Kipnis. 2016. Shedding light on IL-33 in the eye. Journal of Experimental Medicine 213:141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749930/
I.A. Marin and J. Kipnis. 2016. Central Nervous System: (Immunological) ivory tower or not? Neuropsychopharmacology doi: 10.1038/npp.2016.122. [Epub ahead of print]. http://www.nature.com/npp/journal/vaop/ncurrent/full/npp2016122a.html
S.P. Gadani and J. Kipnis. 2016. Natural killers in the brain’s nursery. Nature Neuroscience 19:176-177. http://www.nature.com/neuro/journal/v19/n2/full/nn.4227.html
Ellwardt, J.T. Walsh, J. Kipnis, and F. Zipp. 2016. Understanding the role of T cells in CNS homeostasis. Trends in Immunology 37:154-165. http://www.sciencedirect.com/science/article/pii/S1471490615003051
J.C. Cronk, N.C. Derecki, V. Litfak, and J. Kipnis. 2016. Unexpected cellular players in Rett syndrome pathology. Neurobiology of Disease 92:64-71. http://www.sciencedirect.com/science/article/pii/S0969996115001679
S.E. Adamson, A.K. Meher, Y-H. Chiu, J.K. Sandilos, N.P. Oberholtzer, N.N. Walker, S.R. Hargett, S.A. Seaman, S.M. Peirce-Cottler, B.E. Isakson, C.A. McNamara, S.R. Keller, T.E. Harris, D.A. Bayliss, N. Leitinger. 2015. Pannexin 1-mediated ATP release is required for insulin-stimulated glucose uptake in adipocytes. Molecular Metabolism 4:610-618. (Journal cover and video highlight; selected by F1000). (http://www.sciencedirect.com/science/article/pii/S2212877815001337)
L.S. Shankman, D. Gomez, O.A. Cherepanova, M. Salmon, G.F. Alencar, R.M. Haskins, P. Swiatlowska, A.A. Newman, E.S. Greene, A.C. Straub, B. Isakson, G.J. Randolph, and Owens, G.K. 2015. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nature Medicine 21:628-637. (http://www.nature.com/nm/journal/v21/n6/full/nm.3866.html)
A.M. Fond, C.S. Lee, I.G. Schulman, R.S. Kiss, and K.S. Ravichandran. 2015. Apoptotic cells trigger a new membrane-initiated pathway in macrophages to upregulate ABCA1 expression. Journal of Clinical Investigation 125:2748-2758. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563683/
- Featured on CNN, National Fox News, Daily Progress, and UVa Today
- Faculty of 1000 – recommended article
A.W. Lohman, I.L Leskov, J.T. Butcher, S.R. Johnstone, T.A. Stokes, D. Begandt, L.J. DeLalio, A.K. Best, S. Penuela, N. Leitinger, K.S. Ravichandran, K.Y. Stokes and B.E. Isakson. 2015. Pennexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation. Nature Communications 6:7965. http://www.nature.com/articles/ncomms8965
S.P. Gadani, J.T. Walsh, J.R. Lukens and J. Kipnis. 2015. Dealing with danger in the CNS: The response of the immune system to injury. Neuron 87:47-62. http://www.sciencedirect.com/science/article/pii/S0896627315004262
Louveau, I. Smirnov, T.J. Keyes, J.D. Eccles, S.J. Rouhani, J.D. Peske, N.C. Derecki, D. Castle, J.W. Mandell, K.S. Lee, T.H. Harris and J. Kipnis. 2015. Structural and functional features of central nervous system lymphatic vessels. Nature 523:337-341. http://www.nature.com/nature/journal/v523/n7560/full/nature14432.html
J.T. Walsh, S. Hendrix, F. Boato, I. Smirnov, J. Zheng, J.R. Lukens, S. Gadani, D. Hechler, G. Gölz, K. Rosenberger, T. Kammertöns, J. Vogt, C. Vogelaar, V. Siffrin, A. Radjavi, A. Fernandez-Castaneda, A. Gaultier, R. Gold, T.D. Kanneganti, R. Nitsch, F. Zipp and J. Kipnis. 2015. MHCII-independent CD4+ T cells protect injured CNS neurons vial IL-4. Journal of Clinical Investigation 125:2547. http://www.jci.org/articles/view/76210
J.C. Cronk, N.C. Derecki, E. Ji, Y. Xu, A.E. Lampano, I. Smirnov, W. Baker, G.T. Norris, I.A. Marin, N. Coddington, Y. Wolf, S.D. turner, A. Aderem, A.L. Klibanov, T.H. Harris, S. Jung, V. Litvak and J. Kipnis. 2015. Methyl-CpG binding protein 2 regulates microglia and macrophage gene expression in response to inflammatory stimuli. Immunity 42:679-691. http://www.sciencedirect.com/science/article/pii/S1074761315001272
S.P. Gadani and J. Kipnis. 2015. Brainless immunity no more. Nature Immunology 16:440-441. http://www.nature.com/ni/journal/v16/n5/full/ni.3145.html
S.P. Gadani, J.T. Walsh, I. Smirnov, J. Zheng and J. Kipnis. 2015. The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury. Neuron 84:703-709. http://www.sciencedirect.com/science/article/pii/S0896627315000392
WHAT’S NEW WITH OUR FACULTY?
Dr. Michael J. Guertin, Assistant Professor, Biochemistry and Molecular Genetics
Drs. Yunxian (Fureya) Liu and Michael Guertin from the Department of Biochemistry and Molecular Genetics came in second place in the NCI Challenge grant competition for their “Team Transcription” and are featured on this website. Congratulations Drs. Liu and Guertin.
Dr. Jonathan Kipnis, Professor and Chair, Department of Neuroscience; Center for Brain Immunology and Glia
Dr. Kipnis recently published a review article in Science (Science 353:766-771. 2016) that was featured on the cover of the journal. In the article, he addressed “the current standing of and challenging questions related to interactions between adaptive immunity and the CNS”.
Dr. Wladek Minor, Harrison Distinguished Professor, Department of Molecular Physiology and Biological Physics.
Congratulations to Dr. Wladek Minor, whose research was featured on the cover of Acta Crystalographica Section D Structural Biology (1 November, 2016).
Congratulations to Dr. Edward Egelman, whose work was featured on the cover of the Biophysical Journal (23 February, 2016). The figure “shows a β-sheet formed by strands coming from three different protein subunits in the type VI secretion system sheath from Vibrio cholera. This structure was solved by cryo-EM at a resolution that allowed a full atomic model to be built for the large assembly.” (E.H. Egelman and A. Engel. 2016. Biophysical Journal 110:E01).
Congratulations to Dr. Norbert Leitinger and BIMS/Pharmacology student, Samantha Adamson, whose research was featured on the cover of Molecular Metabolism (September, 2015). The manuscript identifies “Panx1 channels as mediators of controlled extracellular neucloetide release from adipocytes” and shows that “Panx1-dependent ATP release is required for full activation of insulin-induced glucose uptake in adipocytes” and that that “insulin a novel mediator of Panx1 channel activation. (A.E. Adamson, et al., 2016. Molecular Metabolism 4:610-618).
Congratulations to Dr. Judith M. White and BIMS/Cell Biology student Jason Shumaker, whose work was featured on the cover of Science Translational Medicine. (L.M. Johansen, L.E. DeWald, C.J. Shoemaker, B.G. Hoffstrom, C.M. Lear-Rooney, A. Stossel, E. Nelson, S.E. Delos, J.A. Simmons, J.M. Grenier, L.T. Pierce, H. Pajouhesh, J. Lehár, L.E. Hensley, P.J. Glass, J.M. White, and G.G. Olinger. June, 2015. A Screen of Approved Drugs and Molecular Probes Identifies Therapeutics with Anti-Ebolavirus Activity. Sci. Transl. Med. 7:290ra89).