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Brian Wigdahl, PhD

Professor and Chair, Microbiology and Immunology; Director, Institute for Molecular Medicine and Infectious Disease

  • Department:Microbiology and Immunology
  • Education: PhD - Medical College of Wisconsin (1980)
Research Overview

Research interests: Immunopathogenesis and neuropathogenesis of HIV-1 and HTLV-I infection, transcriptional regulation of retroviral expression, viral sequence diversity and correlations to disease, development of microbicidal agents.

Research staff: Michael Nonnemacher, PhD,Vanessa Pirrone, PhD, William, Dampier, PhD, Shendra Passic, MS, Katie Kercher, MS, Jean Williams and Wen Zhong

Graduate students: Satinder Dahiya and Gregory Antell

In the News

Research

Retroviruses have been implicated as causative agents in immunologic dysfunction, malignancy, and a number of progressive neurologic disorders. The overall goal of the research program is to identify molecular mechanisms involved in the pathogenesis of these viral pathogens and to develop strategies to diagnose, prevent, and treat human disease caused by these devastating agents. Ongoing research is focused in three major programmatic areas utilizing molecular, cellular, and modeling technologies involving (1) protein structure and function studies using fluorescence-activated flow cytometry, laser capture and deconvolution fluorescence microscopy, (2) molecular genomics and proteomic strategies, (3) DNA sequencing and genotype analyses, (4) molecular modeling strategies to facilitate design of novel therapeutic agents, (5) DNA-protein biochemistry, (6) methods to assess transcriptional control mechanisms, (7) in vitro cell culture models, (8) viral replication studies utilizing biocontainment safety level 3 (BSL-3) facilities, (9) in vivo animal model systems, and (10) xenografting, cellular trafficking, and quantitative assessment procedures to identify specific uninfected and infected cell populations.

HIV-1 LTR diagram: Modulatory Region, Enhancer Region, Core Region

In the first programmatic area, the molecular mechanisms involved in regulating gene expression of human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS) and the progressive neurologic disorder, HIV-dementia (HIVD), is under exploration. Specifically, the laboratory focuses on the impact of retrovirus genetic variation, signaling pathways, cellular differentiation processes and viral transactivators on critical DNA-protein interactions involved in regulating HIV transcription in cells of monocyte-macrophage origin, including CD34+ precursor cells in the bone marrow and peripheral blood. In addition to defining the transcription regulatory mechanisms that may be critical to the etiology of HIVD, studies are also focused on defining signature sequences in the viral long terminal repeat (LTR) and genes encoding HIV regulatory proteins (Tat and Vpr) that may provide information useful in developing predictive tools to track the development of neurologic disease and therapeutic targets

Retroviruses

In the second area of investigation, molecular modeling strategies and other experimental approaches are being used to develop therapeutic strategies to prevent sexual transmission of HIV. These studies have led to the identification of a family of compounds that interfere with the interaction of HIV-1 gp120 with the receptor (CD4) and the coreceptors (CXCR4 and CCR5).

HTLV-1 Tax Nucleocytoplasmic Shuttling
HTLV-1 Tax Nucleocytoplasmic Shuttling

In the third area of investigation, the role that a selected group of cellular transcription factors (Sp1/Sp3, C/EBP, AP-1, and ATF/CREB) play in regulating Tax-mediated transactivation of the human T cell lymphotropic virus type I (HTLV-I) LTR during hematopoiesis and during development and activation of cells of the monocyte-macrophage origin and other lineages of cells important in cell-mediated immune response to HTLV infection is under investigation. Studies are also in progress to identify nuclear and cytoplasmic proteins involved in nuclear export and secretion of the HTLV-1 oncoprotein Tax. These studies will also identify Tax domains integrally involved in these processes. Defining these molecular interactions will be important to developing new therapeutic strategies to prevent HTLV-I-associated neurologic disease.

Collaborating for Culturally-Competent Care
Professors Jeffrey Jacobson, Jill Foster, Brian Wigdahl and Irwin Chaiken give valuable insight into the pivotal collaborative work they are performing in the ongoing battle against HIV/AIDS. Download PDF File

Publications

Selected Publications
(See all Brian Wigdahl's publications in PubMed.)

"Cocaine alters cytokine profiles in HIV-1 infected African Amerian individuals in the DREXELMED HIV/AIDS Genetic Analysis Cohort"
Parikh N, Dampier W, Feng R, Passic SR, Zhong W, Frantz B, Blakey B, Aiamkitsumrit B, Pirrone V, Nonnemacher MR, Jacobson JM, and B Wigdahl
Journal of Acquired Immune Deficiency Syndromes, in press, 2014

"CCAAT enhancer binding protein and nuclear factor of activated T cells regulate HIV-1 LTR via a novel conserved downstream site in cells of the monocyte-macrophage lineage"
Dahiya S, Liu Y, Nonnemacher MR, and B Wigdahl
PloS One, 9(2): e88116, 2014

"Global NeuroAIDS roundtable"
Joseph J, Achim CL, Boivin MJ, Brew BJ, Clifford DB, Colosi DA, Ellis RJ, Heaton RK, Gallo-Diop A, Grant I, Kanmogne GD, Kumar M, Letendre S, Marcotte TD, Nath A, Pardo CA, Paul RJ, Pulliam L, Robertson K, Royal W 3rd, Sacktor N, Sithinamsuwan P, Smith DM, Valcour V, Wigdahl B, and C Wood
Journal of Neurovirology, 19(1): 1-9, 2013

"Impact of age on markers of HIV-1 disease"
Pirrone V, Libon DJ, Sell C, Lerner CA, Nonnemacher MR, and B Wigdahl
Future Virology, 8(1): 81-101, 2013

"Extracellular HIV-1 viral protein R affects astrocytic glyceraldehyde 3-phosphate dehydrogenase activity and neuronal survival"
Ferrucci A, Nonnemacher MR, and B Wigdahl 
Journal of Neurovirology, 19(3): 239-253, 2013

"Genetic variation and HIV-associated neurologic disease"
Dahiya S, Irish BP, Nonnemacher MR, and B Wigdahl
Advances in Virus Research, 87: 183-240, 2013

"Immunological control of herpes simplex virus infections"
Egan KP, Wu S, Wigdahl B, and SR Jennings
Journal of Neurovirology, 19(4): 328-345, 2013

"Epigenetics, drugs of abuse, and the retroviral promoter"
Shirazi J, Shah S, Sagar D, Nonnemacher MR, Wigdahl B, Khan ZK, and P Jain
Journal of Neuroimmune Pharmacology, 8(5): 1181-1196, 2013

"Macrophage colony stimulating factor regulation by nuclear factor kappa B:  A relevant pathway in human immunodeficiency virus type 1 infected macrophages"
Kogan M, Haine V, Ke Y, Wigdahl B, Fischer-Smith T, and J Rappaport
DNA and Cell Biology, 31(3): 278-288, 2012

"Extracellular human immunodeficiency virus type 1 viral protein R causes a reduction in ATP and glutathione levels in an astrocytic cell line resulting in a compromised antioxidant reservoir"
Ferrucci A, Nonnemacher MR, Cohen EA, and B Wigdahl
Virus Research, 167(2): 358-369, 2012

"Deployment of the HIV-1 protein arsenal: Combating the host to enhance viral transcription and providing targets for therapeutic development"
Dahiya S, Nonnemacher MR, and B Wigdahl
J. General Virology, 93: 1151-1172, 2012

"Impact of Tat genetic variation on HIV-1 disease"
Li L, Dahiya S, Kortagere S, Cunningham D, Pirrone V, Nonnemacher M, and B Wigdahl
Advances in Virology, Volume 2012, Article ID 123605, 2012

"Substance abuse, HIV-1 and hepatitis"
Parikh N, Nonnemacher MR, Pirrone V, Block T, Mehta A, and B Wigdahl
Current HIV Research, 10(7): 557-571, 2012

"A nipple shield delivery system of oral drug delivery to breastfeeding infants:  Microbicide delivery to inactivate HIV"
Gerrard SE, Baniecki ML, Sokal DC, Morris MK, Urdaneta-Hartmann S, Krebs FC, Wigdahl B, Abrams BF, Hanson CV, Slater NK, and AD Edwards
International Journal of Pharmacology, 434(1-2): 224-234, 2012.

"Decreased cervical epithelial sensitivity to nonoxynol-9 (N-9) after four daily applications in a murine model of topical vaginal microbicide safety"
Lozenski K, Ownbey R, Wigdahl B, Kish-Catalone T, and FC Krebs
BMC Pharmacology and Toxicology, 13: 9, 2012

Teaching

Dr. Wigdahl is professor and chair of the Department of Microbiology & Immunology at Drexel University College of Medicine.

Research Locations

Department of Microbiology & Immunology
2900 Queen Lane
Philadelphia, PA 19129
Phone: 215-991-8352
Fax: 215-848-2271

Department of Microbiology & Immunology
245 N. 15th Street
Philadelphia, PA 19102
Phone: 215-762-7598
Fax: 215-762-1955

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