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

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

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 / 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

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

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.

Funding News

The College of Medicine’s Brian Wigdahl, PhD, professor and chair of microbiology and immunology, and Michael Nonnemacher, PhD, professor of microbiology and immunology, received funding from National Institutes of Health (NIH)’s Martin Delaney Collaboratories for HIV Cure Research Program. Their combined total awards were $2.4 million.

“Sidney Kimmel Cancer Center Research Consortium: Committed to Changing the Cancer Landscape in Philadelphia”
Pulse (Spring 2024)

Editing Genes to Cure HIV
Exel - Drexel University Research Magazine (2023)

Ahead of the Game
Exel - Drexel University Research Magazine (2019)

Co-investigators to Study Anal Dysplasia Among HIV-Infected Individuals
(November 2, 2017)

Faculty Highlights: Grants and Awards From Summer 2017
Drexel Now (October 11, 2017)

Symposium to Address Treatment and Prevention of Infectious Inflammatory and Oncogenic Disease
College of Medicine Newsroom (June 5, 2014)

Cognitive Secrets"
Exel - Drexel University Research Magazine (2013)

Brian Wigdahl, PhD, Named 2013 Pioneer in NeuroVirology
College of Medicine Newsroom (December 13, 2013)

College of Medicine Hosts Symposium to Address Treatment and Prevention of Infectious Disease
College of Medicine Newsroom (June 6, 2013)

"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.