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Brian Wigdahl

Brian Wigdahl, PhD

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


Department: Microbiology & Immunology

Education

  • PhD - Medical College of Wisconsin (1980)

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

Research Overview

Junior faculty: Vanessa Pirrone, PhD, William Dampier, PhD, Shendra Passic, MS

Graduate students: Robert Link (5th-year PhD), Theodore Gurrola (3rd-year PhD)

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

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
  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

HIV-1 LTR / 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 [PDF]

Professors Jeffrey Jacobson, Brian Wigdahl and Irwin Chaiken give valuable insight into the pivotal collaborative work they are performing in the ongoing battle against HIV/AIDS.

In the Media

Publications

"Functional studies of CCAAT/enhancer binding protein site located downstream of the transcriptional start site"
Liu, Y., Nonnemacher, M. R., Alexaki, A., Pirrone, V., Banerjee, A., Li, L., Kilareski, E., and B. Wigdahl
Clinical Medicine Insights: Pathology, 10: 1-10, 2017. PMID: 29162980. DOI: 10.1177/1179555717694556.

"Designing broad-spectrum anti-HIV-1 gRNAs to target patient-derived variants"
Dampier, W., Sullivan, N. T., Chung, C-H, Mell, J.C., Nonnemacher, M. R., and B. Wigdahl
Scientific Reports, 7(1):14413, 2017. PMID: 29089503. DOI: 10.1038/s41598-017-12612-z.

"Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow"
Nonnemacher, M.R#., Quiterio, S#., Allen, A.G., Mele, A.R., Pirrone, V., and B. Wigdahl
Biology of Myelomonocytic Cells, May 10, 2017. DOI: 10.5772/67596. #Authors contributed equally.

"Broad spectrum and personalized gRNAs for CRISPR/Cas9 HIV-1 therapeutics"
Dampier, W#., Sullivan, N. T#., Mell, J. C., Pirrone, V., Ehrlich, G., Cheng-Han C., Allen, A. G., DeSimone, M., Zhong, W., Kercher, K., Passic, S., Williams, J. W., Szep, Z., Khalili, K., Jacobson, J. M., Nonnemacher, M. R., and B. Wigdahl
AIDS Res Hum Retroviruses, 34(11):950-960, 2018. PMID: 29968495. DOI: 10.1089/AID.2017.0274 #Authors contributed equally.

"Prediction of HIV-1 subtype-specific off-target effects arising from CRISPR/Cas9 gene editing therapy"
Link, R.W., Nonnemacher, M.R., Wigdahl, B., and Dampier, W
The CRISPR Journal, 1(4):294-302, 2018. PMID:31021222. DOI: 10.1089/crispr.2018.0020

"Gene editing of HIV-1 co-receptors to prevent and/or cure virus infection"
Allen, A. G., Chung, C-H., Atkins, A., Dampier, W., Khalili, K., Nonnemacher, M.R., and B. Wigdahl
Frontiers in Microiology, 9:2940, 2018. PMID: 30619107. DOI: 10.3389/fmicb.2018.02940

"CRSeek: a Python module for facilitating complicated CRISPR design strategies"
Dampier, W., Chung, C., Sullivan, N.T., Atkins, A.J., Nonnemacher, M.R., and B. Wigdahl
PeerJ Preprints, 6:e27094v1, 2018. https://doi.org/10.7287/peerj.preprints.27094v1

"Novel gRNA design pipeline to develop broad-spectrum CRISPR/Cas9 gRNAs for safe targeting of the HIV-1 quasispecies in patients"
Sullivan, N. T#., Dampier, W#., Allen, A., Chung, C., Allen, A. G., Atkins, A., Pirrone, V., Homan, G., Passic, S., Williams, J., Zhong, W., Kercher, K., Desimone, M., Li, L., Antell, G., Mell, J. C., Ehrlich, G.D., Szep, S., Jacobson, J., Nonnemacher, M. R., and B. Wigdahl
Scientific Reports, 9(1): 17088, 2019. PMID: 31745112. DOI: 10.1038/s41598-019-52353-9. #Authors contributed equally.

"Computational analysis concerning the impact of DNA accessibility on CRISPR-Cas9 cleavage efficiency"
Chung, C-H., Allen, A., Sullivan, N.T., Atkins, A., Nonnemacher, M.R., Wigdahl, B., and W. Dampier
Molecular Therapy, 28(1):19-28, 2020. PMID: 31672284. DOI: 10.1016/j.ymthe.2019.10.008

"Integrated human immunodeficiency virus type 1 sequence in J-Lat 10.6"
Chung, C.H#., Mele, A. R#., Allen, A.G., Costello, R., Dampier, W., Nonnemacher, M.R., and B. Wigdahl
Microbiology Resource Announcement, 9(18):e00179-20, 2020. PMID: 32354973. DOI: 10.1128/MRA.00179-20. #Authors contributed equally.

"Safe CRISPR/Cas9 inactivation of HIV-1 transcription with high specificity and broad-spectrum activity in latently infected cells by mutation of HIV-1 promoter NF-kB binding sites"
Chung, C-H#., Allen, A.G#., Atkins, A., Sullivan, N.T., Homan, G., Costello, R., Madrid, R., Nonnemacher, M.R., Dampier, W., and B. Wigdahl
Molecular Therapy Nucleic Acids, 21:965, 2020. PMID: 32818921. DOI: 10.1016/j.omtn.2020.07.016. #Authors contributed equally.

"Designing Safer CRISPR/Cas9 Therapeutics for HIV: Defining Factors That Regulate and Technologies Used to Detect Off-Target Editing"
Sullivan, N. T#., Allen, A. G#., Atkins, A., Chung, C-H., Dampier, W., Nonnemacher, M.R., and B. Wigdahl
Frontiers in Microbiology, 11:1872, 2020. PMID: 32903440. DOI: 10.3389/fmicb.2020.01872. #Authors contributed equally.

"HIV-1 cure strategies: Why CRISPR?"
Atkins, A. J., Allen, A, G., Dampier, W., Haddad, E. K., Nonnemacher, M.R., and B. Wigdahl
Expert opinion in Biological Therapy, 21:6, 781-793, 2021. PMID: 33331178. DOI: 10.1080/14712598.2021.1865302

"Computational Design of gRNAs Targeting Genetic Variants Across HIV-1 Subtypes for CRISPR-Mediated Antiviral Therapy"
Chung, C-H., Allen, A.G., Atkins, A., Link, R.W., Nonnemacher, M.R., Dampier, W., and B. Wigdahl
Frontiers in Cellular and Infection Microbiology, 11:94, 2021. PMID: 33768011. DOI: 10.3389/fcimb.2021.593077.


Contact Information


Department of Microbiology & Immunology
2900 W. 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