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

Professor, Department of Laboratory Medicine & Pathology

E-MAIL: clark002@umn.edu

Research Interests:

My research interests are in the neuropathological study of degenerative neurological diseases, particularly hereditary ataxias and the CNS manifestations of myotonic dystrophy.  I am actively collaborating with the laboratories of Harry Orr, Laura Ranum and John Day on these projects.  I am studying both the human forms of these diseases as well as transgenic models in which human mutations are expressed in mice.  The focus of my laboratory is on structural pathological changes using immunohistochemical techniques.

Selected Publications:

(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)

Goodwin M, Mohan A, Batra R, Lee KY, Charizanis K, Gómez FJ, Eddarkaoui S, Sergeant N, Buée L, Kimura T, Clark HB, Dalton J, Takamura K, Weyn-Vanhentenryck SM, Zhang C, Reid T, Ranum LP, Day JW, Swanson MS. MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain. Cell Rep. 2015 Aug 18;12(7):1159-68.

Hubbard M, Qaiser R, Clark HB, Tummala R. Multiple calcifying pseudoneoplasms of the neuraxis. Neuropathology. 2015 Mar 30.

Öz G, Kittelson E, Demirgöz D, Rainwater O, Eberly LE, Orr HT, Clark HB. Assessing recovery from neurodegeneration in spinocerebellar ataxia 1: Comparison of in vivo magnetic resonance spectroscopy with motor testing, gene expression and histology. Neurobiol Dis. 2015 Feb;74:158-66.

Olin MR, Low W, McKenna DH, Haines SJ, Dahlheimer T, Nascene D, Gustafson MP, Dietz AB, Clark HB, Chen W, Blazar B, Ohlfest JR, Moertel C. Vaccination with dendritic cells loaded with allogeneic brain tumor cells for recurrent malignant brain tumors induces a CD4(+)IL17(+) response. J Immunother Cancer. 2014 Feb 18;2:4.

Ebner BA, Ingram MA, Barnes JA, Duvick LA, Frisch JL, Clark HB, Zoghbi HY, Ebner TJ, Orr HT. Purkinje cell ataxin-1 modulates climbing fiber synaptic input in developing and adult mouse cerebellum. J Neurosci. 2013 Mar 27;33(13):5806-20.

Bazerbachi F, Maiser S, Clark HB. Giant thoracic schwannoma masquerading as transverse myelitis. QJM. 2013 Aug;106(8):759-61.

Charizanis K, Lee K-Y,  Batra R, Goodwin M, Zhang C, Yuan Y, Shiue L, Cline M, Scotti, MM, Xia G, Kumar A, Ashizawa T, Clark HB, Kimura T, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Gomez-Pereira M, Gourdon G, Sakai N, Nishino S, Ares M, Darnel RB, and Swanson MS. Muscleblind-Like 2 Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy.  Neuron  2012 (in press)

Öz G, Vollmers ML, Nelson CD,  Shanley R, Eberly LE, Orr HT and Clark HB.  In vivo monitoring of recovery from neurodegeneration in conditional transgenic SCA1 mice.  Experimental Neurology 232:290-298, 2011.

Ingram MA, Orr HT, Clark HB. Genetically engineered mouse models of the trinucleotide-repeat spinocerebellar ataxias. Brain Res Bull. 2011 Jul 23.

Paciorkowski AR, Shafrir Y,  Hrivnak J, Patterson MC,  Tennison MB, Clark HB, Dobyns WB, and Gomez CM: Massive expansion of SCA2: A progressive encephalopathy with infantile spasms, retinitis pigmentosa, and autonomic dysfunction.  Neurology 77:1055-60, 2011.

Zu T, Gibbens B, Moncada N, Gomez-Pereira M, Margolis J, Nan Z, Low W, Somia N, Swanson MS, Clark HB, Schmechel S, Gourdon G, Moseley M and Ranum LPW: Non-ATG Initiated Translation Directed by Microsatellite Repeat Expansions.  PNAS 108: 260-5, 2011.

Iltis IV, Hutter D, Bushara KO, Clark HB, Gross MD, Eberly LE, Gomez CM and Oz G: ¹H MR Spectroscopy in Friedreich's Ataxia and Ataxia with Oculomotor Apraxia Type 2.  Brain Research  1358: 200-210, 2010.

Oz G, Nelson CD, Koski DM, Henry P-G, Marjanska M, Deelchand DK, Shanley R, Eberly LE, Orr HT and Clark HB: Noninvasive detection of pre-symptomatic and progressive neurodegeneration in a mouse model of spinocerebellar ataxia type 1.  J Neuroscience. 30(10):3831–3838, 2010.

Oz G, Hutter D, Tkaci I, Clark HB, Gross MD, Jiang H, Eberly LE, Bushara KO and Gomez CM: Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status.  Movement Disorders 25:1253-1261, 2010.

Jorgensen ND, Andresen MJ, Lagalwar S, Armstrong B, Stevens S, Byam CE, Duvick LA, Lai S, Jafar-Nejad P, Zoghbi HY, Clark HB and Orr HT: Phosphylation of ATXN1 at S776 in the cerebellum.  J. Neurochem. 110:675-686, 2009.

Carlson KM, Melcher L, Zoghbi  HY, Clark HB, and Orr HT. Characterization of the zebrafish ATXN1/AXH gene family. J. Neurogenetics 23:313-23, 2009.

Ryan LJ, Bowman R, Zantek ND, Sherr G, Maxwell R, Clark HB, Mair DC. Use of therapeutic plasma exchange in the management of acute hemorrhagic leukoencephalitis: a case report and review of the literature. Transfusion. 2007 Jun;47(6):981-6.

Kendi AT, McKinney AM, Clark HB, Kieffer SA. A pediatric case of low-grade lymphomatoid granulomatosis presenting with a cerebellar mass. AJNR Am J Neuroradiol. 2007 Oct;28(9):1803-5.

Ryan LJ, Bowman R, Zantek ND, Sherr G, Maxwell R, Clark HB, Mair DC. Use of therapeutic plasma exchange in the management of acute hemorrhagic leukoencephalitis: a case report and review of the literature. Transfusion. 2007 Jun;47(6):981-6. Review.

Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, Lysholm A, Burright E, Zoghbi HY, Clark HB, Andresen JM, Orr HT. RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell. 2006 Nov 17;127(4):697-708.

He Y, Zu T, Benzow KA, Orr HT, Clark HB, Koob MD. Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits. J Neurosci. 2006 Sep 27;26(39):9975-82.

Ikeda Y, Dick KA, Weatherspoon MR, Dalton JC, Stevanin G, Durr A, Zuhlke C, Burk K, Brice A, Clark HB, Schut LJ, Day JW, Ranum LPW: Spectrin mutations cause spinocerebellar ataxia type 5. Nature Genetics 38:184-190, 2006

Kordasiewicz HB, Thompson RM, Clark HB, and Gomez CM: C-termini of P/Q-type Ca2+ channel of alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity. Hum. Mol. Genetics 15: 1587-1599, 2006.

Moseley ML, Zu T, Ikeda Y, Gao W, Mosemiller AK, Daughters R, Chen G, Weatherspoon MR, Clark HB, Ebner TJ, Day JW and Ranum LPW: Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nature Genetics, 38:758-769, 2006.

H. Brent Clark