Graduate Studies Faculty

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Vivek K. Unni, M.D., Ph.D.

Assistant Professor
Admin Unit: Parkinson Center of Oregon
Neuroscience Graduate Program
Research Interests:
Parkinson’s Disease, alpha-synuclein, protein aggregation and degradation, neurodegeneration, in vivo imaging, clinical neurology, movement disorders, Neurobiology of Disease
Preceptor Rotations
Dr. Unni has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Unni has not indicated availability as a mentor at this time.

Dr. Unni was raised in Ohio and received his undergraduate training in Chemistry and Biological Sciences at Stanford University. He earned his M.D., Ph.D. from Columbia University’s College of Physicians & Surgeons in 2003, where his thesis work focused on mechanisms of synaptic plasticity in the rodent hippocampus. After completing an internship in Internal Medicine at St. Luke’s – Roosevelt Hospital in New York, he moved to Boston where he finished neurology residency and fellowship in movement disorders in the combined Harvard Partners program (Brigham & Women’s Hospital and Massachusetts General Hospital). After completing fellowship, he was on staff in the Movement Disorders Division of the Department of Neurology at MGH and an instructor at Harvard Medical School until his arrival at OHSU in the fall of 2011. Dr. Unni is currently an assistant professor in the Department of Neurology, a PI in the Jungers Center for Neurosciences Research and a clinical neurologist in the Parkinson Center of Oregon.

The goal of my research is to understand how the protein alpha-synuclein is involved in Parkinson’s disease (PD) and related disorders like Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Recent progress in the field has taught us that many neurodegenerative diseases are caused by the abnormal aggregation and accumulation of specific proteins. Although the exact protein in each disease varies (e.g. beta-amyloid and tau in Alzheimer’s Disease, tau and TDP-43 in forms of Fronto-temporal Dementia and Amyotrophic Lateral Sclerosis, huntingtin in Huntington’s Disease, etc.) there remains a common theme of abnormal aggregation and deposition of the disease-specific protein in each case. Understanding this process at a deep level promises to revolutionize how we think about the causes of each of these disorders and offers the potential for developing new therapeutics for this devastating group of neurological diseases. Of all these diseases, the best evidence that simply increasing the specific protein level can cause disease exists for PD and DLB. This is because numerous lines of evidence from human genetic studies point to increased levels of wild-type alpha-synuclein being sufficient to cause PD and DLB. One of these lines of evidence is that duplication (or triplication) of the SCNA locus coding for alpha-synuclein, which increases alpha-synuclein levels by the seemingly modest amount of 50% (or 100%), causes patients to develop PD and/or DLB. The goal of my work is to use mouse models of PD and DLB, where alpha-synuclein is over-expressed, to understand in the living brain how increasing levels of this protein leads to its aggregation and subsequent neuronal dysfunction and cell death.

One hypothesis for how this could occur is that increased alpha-synuclein levels by itself causes this protein self-aggregate to form potentially toxic species that then cause neurons to die. This simple scenario is complicated, however, by the fact that alpha-synuclein can form many different kinds of aggregates, some of which are potentially toxic and others which could be protective. The ability to test this and related hypotheses in the living brain would greatly benefit from the development of new experimental strategies to visualize alpha-synuclein in vivo, its metabolism, aggregation and the consequences of these processes for neurons. For these reasons I have spent the past several years, first at Harvard Medical School and Massachusetts General Hospital and now at OHSU, developing new approaches to try and tackle these difficult problems. Our work allows us (for the first time) to visualize alpha-synuclein in the living brain in mouse models of PD and DLB using in vivo multiphoton fluorescence microscopy through “cranial windows.”

Our recent data demonstrate that we can visualize human wild-type alpha-synuclein fused to enhanced Green Fluorescent Protein in the cortex of transgenic mice with cellular and synaptic resolution using this cranial window-based approach. Furthermore, we can follow individually labeled neurons or presynaptic terminals serially over a period of many months and obtain measurements of alpha-synuclein mobility in vivo in these compartments. We have also developed treatment paradigms for applying agonists or antagonists of different relevant pathways directly to the cells that are being imaged in vivo and for recovering treated tissue in order to do further biochemical analysis. Using these approaches, we are currently studying the mechanisms of alpha-synuclein aggregation and degradation in the living brain. Specifically, we have been probing the role of the two main protein degradation pathways known, the ubiquitin-proteasome system and autophagy, in the degradation of alpha-synuclein in vivo, currently an unanswered question in the field. In addition, we are studying the role of environmental toxins implicated in PD pathogenesis on the aggregation of alpha-synuclein in vivo and the subsequent neuronal dysfunction this causes.
Spinelli KJ, Taylor JK, Osterberg VR, Churchill MJ, Pollock E, Moore C, Meshul CK, Unni VK (2014) Presynaptic alpha-synuclein aggregation in a mouse model of Parkinson's disease. J Neurosci, 34:2037-50.
Ebrahimi-Fakhari D, McLean PJ, Unni VK (2012) Alpha-synuclein's degradation in vivo: Opening a new (cranial) window on the roles of degradation pathways in Parkinson disease. Autophagy, Feb 1;8:281-3.
Ebrahimi-Fakhari D, Cantuti-Castelvetri I, Fan Z, Rockenstein E, Masliah E, Hyman BT, McLean PJ and Unni VK. (2011) Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of α-synuclein. J Neurosci, 31:14508-14520.
Unni VK, Ebrahimi-Fakhari D, Vanderburg CR, McLean PJ and Hyman BT (2011). Studying protein degradation pathways in vivo using a cranial window-based approach. Methods Mar; 53(3):194-200.
Unni VK, Weissman TA, Rockenstein E, Masliah E, McLean PJ and Hyman BT (2010). In vivo imaging of alpha-synuclein in mouse cortex demonstrates stable expression and differential subcellular compartment mobility. PLoS ONE May 11; 5(5):e10589.