H. Brent Clark M.D., Ph.D.

Professor
Director, Neuropathology Services at University of Minnesota Medical Center, Fairview
612-625-7636
clark002@umn.edu

In addition to a full-time practice at University of Minnesota Medical Center, Fairview, Dr. Clark is a consultant at Hennepin County Medical Center and the Minneapolis Veterans Affairs Medical Center.  He is active in the teaching of pathology residents on both the anatomic pathology and neuropathology specialty rotations.  Residents from the Departments of Neurology and Neurosurgery rotate on his service and he teaches a lecture series for both programs.  He also directs the neuropathology section of the second year medical student pathology course.

Educational Background

• Washington University School of Medicine, St. Louis, MO (1978), M.D./Ph.D.
• Barnes Hospital / Washington University, St. Louis, MO (1982), Residency (Anatomic Pathology and Neuropathology)

Board Certification

Anatomic Pathology, Neuropathology

Research Interests

Dr. Clark’s research activities involve pathological studies of cerebellar ataxia both in human disease and experimental animal models. He is a co-investigator on a NIH R01 grant entitled "Molecular genetics of the SCA1 locus," and Director of the Neuropathology Core for the Bob Allison Ataxia Research Center at the University of Minnesota.  

Publications

Dr. Clark has written on a number of subjects, including ataxia, middle cerebral artery dissection, tauopathies, treatment of brain tumors with stereotactic radiosurgery, and increased expression of nitric oxide synthase and cyclo-oxygenase-2 related to cerebral ischemic injury,.  He is a member of the Editorial Board of Brain Pathology and Human Pathology and an ad hoc reviewer for numerous other scientific journals including the Journal of Neuropathology and Experimental Neurology, The American Journal of Pathology, Journal of Neuroscience, and Neurobiology of Disease.

• Feddersen RM, Ehlenfeldt R, Yunis WS, Clark HB and Orr HT: Disrupted cerebellar development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. Neuron, 9:955-966, 1992.
• Hsiao KK, Olson K, Borchelt DR, Johannsdottir R, Shen J, Yunis WS, Xu S, Diedrich J, Kitt C, Sisodia S, Price D, Clark HB and Iadecola C: Cortico-limbic dysfunction in transgenic mice expressing mutant amyloid precursor proteins. Neurobiology of Aging 15:313, 1994.
• Feddersen RM, Clark HB, Yunis WS and Orr HT: In vivo viability of postmitotic Purkinje neurons requires pRb family member function. Molecular and Cellular Neuroscience 6:153-167, 1995.
• Burright EN, Clark HB, Servadio A, Matilla T, Feddersen RM, Yunis WS, Duvick LA, Zoghbi H, and Orr HT: SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell 82:937-948.
• Hsiao KK, Borchelt DR, Olson K, Johannsdottir R, Kitt C, Yunis W, Xu S, Eckman C, Younkin S, Price D, Iadecola C, Clark HB, and Carlson G: Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 15:1203-1218, 1995.
• Orr HT and Clark HB: Biology of Disease: Genetic approaches to pathogenesis of neurodegenerative diseases. Lab. Invest. 73:161-171, 1995.
• Iadecola C, Zhang F, Casey R, Clark HB and Ross ME: Inducible nitric oxide synthase gene expression in vascular cells following transient focal cerebral ischemia. Stroke 27:1373-1380, 1996.
• Feddersen RM, Yunis WS, O'Donnell MA, Ebner TJ, Shen L, Iadecola C, Orr HT, and Clark HB: Susceptibility to cell death induced by mutant SV40 T-antigen correlates with Purkinje neuron functional development. Molecular and Cellular Neuroscience 9:42-62, 1997.
• Burright EN, Orr HT and Clark HB: Mouse models of human CAG repeat disorders. Brain Pathology 7:965-977, 1997.
• Clark HB, Burright EN, Yunis WS, Larson S, Wilcox C, Hartman B, Matilla A, Zoghbi HY, and Orr HT: Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors followed by progressive cerebellar dysfunction and histological alterations. J . Neuroscience 17(19):7385-7395, 1997.
• Gomez CM, Thompson RM, Gammack JT, Perlman SL, Dobyns WB, Truwit CL, Zee DS, Clark HB and Anderson JH: Spinocerebellar ataxia type 6: Gaze-evoked and vertical nystagmus, Purkinje cell degeneration, and variable age of onset. Ann. Neurol. 42:933-950, 1997.
• Yang G, Zhang F, Feddersen RM, Clark HB and Iadecola C: Cerebellar vascular and synaptic responses in normal mice and in transgenics with Purkinje cell dysfunction. Am. J. Physiol. (Regulatory Integrative Comp. Physiol. 43): R529-R540, 1998.
• Klement IA, Skinner PJ, Kaytor MD, Yi H, Hersch SM, Clark HB, Zoghbi HY and Orr HT: Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95:1-20, 1998.
• Iadecola C, Forster C, Nogawa S, Clark HB and Ross ME: Cyclooxygenase-2 immunoreactivity in the human brain following cerebral ischemia. Acta Neuropathologica 98:9-14, 1999.
• Clark HB and Orr HT: Spinocerebellar ataxia type 1 -- Modeling the pathogenesis of a polyglutamine neurodegenerative disorder in transgenic mice. J. Neuropathol. Expt. Neurol : 59:265-270, 2000.
• Skinner PJ, Vierra-Green CA, Clark HB, Zoghbi HY, and Orr HT: Altered trafficking of membrane proteins in Purkinje cells of SCA1 transgenic mice. Amer. J. Pathol. 159:905-913, 2001.
• Emamian ES, Kaytor MD, Duvick LA, Zu T, Tousey SK, Zoghbi HY, Clark HB and Orr HT. Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron 38:375-387, 2003.
• Zu,T., Duvick, L.A., Kaytor, M.D., Berlinger, M., Zoghbi, H.Y., Clark, H.B. and Orr, H.T., Recovery from Polyglutamine-Induced Neurodegeneration in Conditional SCA1Transgenic Mice. J Neuroscience 24:8853-8861, 2004