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James D. Gorham, M.D., Ph.D.

Title(s):
Professor of Pathology
Professor of Microbiology and Immunology

Department(s):
Pathology
Microbiology and Immunology

Education:
New York University School of Medicine, MD 1992
New York University, PHD 1991
New York University, MS 1989
Haverford College, BA 1984




Dr. Gorham received his B.A. in Biology from Haverford College in 1984, his Ph.D. in Biochemistry from New York University in 1991 and his M.D. from New York University in 1992. He did postdoctoral training at Washington University, where he also completed a residency in Clinical Pathology and was Chief Resident (1997 - 1998). In 1998, he joined Dartmouth Medical School as Assistant Professor in the Department of Pathology with a secondary appointment in the Department of Microbiology and Immunology. He was promoted to Associate Professor in 2004 and to Professor in 2010.

Programs:
Center for Continuing Education in the Health Sciences

Curriculum Vitae:
Gorham_J_CV_2009-02-12.pdf

NIH Biosketch:
Gorham_J_BIO_2009-02-12.pdf

Websites:
http://dms.dartmouth.edu/immuno/faculty/gorham.shtml
http://dms.dartmouth.edu/dgml/contact/

Contact Information:

Dartmouth Medical School
Department of Pathology, HB 7600
1 Medical Center Drive
Lebanon NH 03756

Phone: 603-650-8373
Fax: 603-650-6120
Email: James.D.Gorham@Dartmouth.EDU

Assistant: Christine Kretowicz
Asst. Phone: 603-650-8266
Asst. Email: Christine.Kretowicz@Dartmouth.edu


Professional Interests:

REGULATION OF T HELPER CELLS IN THE HEPATIC IMMUNE SYSTEM

The principal research goal in our laboratory is to understand the biological mechanisms regulating T helper cells, immune tolerance, and autoimmunity in the liver.

Our laboratory has shown that TGF-beta1 is a master regulator of liver immunity. TGF-beta1-deficient mice on the BALB/c background develop an aggressive inflammatory liver pathology that mimics many aspects of the human disease autoimmune hepatitis (AIH). We have shown that liver disease in BALB/c-TGF-beta1-/- mice is dependent upon the genetic background of the mouse, CD4+ T helper cells, and the inflammatory Th1 cytokine IFN-gamma. Our goals are to define the genetic, cellular, and molecular determinants of disease in this mouse model of AIH.

Because of the central role of TGF-beta1 in regulating Th1 mediated autoimmune disease in the liver, we are examining the mechanisms by which TGF-beta1 regulates T helper cell function in vitro. In particular, we are using a variety of approaches to better understand the effects of TGF-beta1 on T helper cell differentiation along the Th1 differentiation pathway. Recent data from our laboratory indicate that TGF-beta1 utilizes multiple mechanisms to inhibit the expression of hepatotoxic Th1 cytokines such as IFN-gamma and TNF-alpha.

Several additional projects are underway to better understand the behavior, trafficking, and regulation of T helper cells in the liver. We are using TCR transgenic mice to understand how antigen stimulation regulates T cells in the liver. In addition we are probing the cellular and molecular characteristics of liver T cells to gain insight into their unique properties.

Grant Information:

"Chemokines in Autoimmune Hepatitis" R01 AI078195

Courses Taught:

Organizer and lecturer of Autoimmunity block, DMS MCB Graduate Course 146 (Immunotherapy)
Lecturer, DMS Year 1 - General Pathology
Small group discussion leader, DMS Year 1 - Medical Immunology


Selected Publications:

 

Gorham JD, Ranson MS, Smith JC, Gorham BJ, Muirhead KA
1 + 1 = 3: Development and validation of a SNP-based algorithm to identify genetic contributions from three distinct inbred mouse strains.
J Biomol Tech 2012 Dec; 23(4):136-46
PMID: 23204929

Cripps JG, Celaj S, Burdick M, Strieter RM, Gorham JD
Liver inflammation in a mouse model of Th1 hepatitis despite the absence of invariant NKT cells or the Th1 chemokine receptors CXCR3 and CCR5.
Lab Invest 2012 Oct; 92(10):1461-71
PMID: 22906987

Cripps JG, Gorham JD
MDSC in autoimmunity.
Int Immunopharmacol 2011 Jul; 11(7):789-93
PMID: 21310255

Cripps JG, Wang J, Maria A, Blumenthal I, Gorham JD
Type 1 T helper cells induce the accumulation of myeloid-derived suppressor cells in the inflamed Tgfb1 knockout mouse liver.
Hepatology 2010 Oct; 52(4):1350-9
PMID: 20803559

Milks MW, Cripps JG, Lin H, Wang J, Robinson RT, Sargent JL, Whitfield ML, Gorham JD
The role of Ifng in alterations in liver gene expression in a mouse model of fulminant autoimmune hepatitis.
Liver Int 2009 Oct; 29(9):1307-15
PMID: 19490417

Robinson RT, Wang J, Cripps JG, Milks MW, English KA, Pearson TA, Gorham JD
End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas.
J Immunol 2009 Mar 1; 182(5):3278-84
PMID: 19234226

Ahonen CL, Wasiuk A, Fuse S, Turk MJ, Ernstoff MS, Suriawinata AA, Gorham JD, Kedl RM, Usherwood EJ, Noelle RJ
Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines.
Blood 2008 Mar 15; 111(6):3116-25
PMID: 18202224

Robinson RT, Gorham JD
TGF-beta 1 regulates antigen-specific CD4+ T cell responses in the periphery.
J Immunol 2007 Jul 1; 179(1):71-9
PMID: 17579023

Park IK, Letterio JJ, Gorham JD
TGF-beta 1 inhibition of IFN-gamma-induced signaling and Th1 gene expression in CD4+ T cells is Smad3 independent but MAP kinase dependent.
Mol Immunol 2007 Jul; 44(13):3283-90
PMID: 17403540

Robinson RT, French MA, Kitzmiller TJ, Gorham JD
Restriction of the CD4+ T-cell receptor repertoire prevents immune pathology in TGF-beta1 knockout mice.
Lab Invest 2006 Aug; 86(8):815-28
PMID: 16751781