Department of Microbiology
Perelman School of Medicine
University of Pennsylvania
402C Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104
TEL 215 573-2773
LAB 215 746-6526
FAX 215 573-4446
My laboratory studies the cellular immune response to pathogens in humans,
non-human primates, and mice. Our primary interest focuses on the role of
HIV-specific T cell responses in HIV infected individuals. These responses
are crucially important in controlling HIV infection, yet the precise characteristics,
mechanisms, and ultimate shortcomings of this response are not well understood.
We also study the immune response against a variety of other human pathogens,
including Epstein-Barr virus, cytomegalovirus, influenza, and other pathogens
of interest. We are also very interested in characterizing the immune response
induced by vaccine agents, including DNA, Adenovirus, and MVA vaccine vector
platforms, in various animal models and humans. Understanding how vaccine-induced
responses relate to natural (pathogen-induced) responses is critical to understanding
the mechanism of vaccine-induced protection.
Human T lymphocytes have numerous functions, including the ability to produce
various cytokines and chemokines, as well as mediate cell death through perforin-
or fas-mediated cytotoxicity. Our research utilizes the most advanced techniques
to directly measure human T lymphocyte responses through the use of polychromatic
flow cytometry, which allows for the simultaneous examination of up to 24
separate parameters on lymphocytes. This multiparametric approach is exceptionally
powerful, and has allowed us to begin identifying correlates of immune protection
in HIV infection, a critical step towards understanding the requirements
of a protective HIV vaccine.
Current Rotation Projects
Given the necessity to learn flow cytometry to work within the lab, rotation
projects generally are gauged on the flow experience of the rotation student.
-Students with no prior experience with flow cytometry will learn basic
four-color (FACS Calibur) flow cytometry initially, in the context of characterizing
immune responses to CMV, EBV, and Influenza from normal donors. The rotation
will culminate with advancing these techniques to 12+-color (BD LSRII) flow
cytometric analysis. At the conclusion of the rotation, students should expect
to have mastered basic flow cytometry, gained significant experience with
multi-color flow cytometry, and learned the proper techniques to measure
pathogen-specific T cell responses by flow cytometry.
-Students with significant flow cytometry experience will be advanced directly
to performing multi-color flow analysis for a number of projects within the
lab. These include:
1. Characterization of HIV-specific immune responses in the setting of various
disease states (acute, chronic, non-progressive, treated, etc).
2. Characterization of immune responses induced by vaccine agents in mice,
non-human primates, and humans.
3. Studying the relationship between HIV genetic diversity and HIV-specific
T cell responses.
4. Defining novel correlates of immune protection against viral diseases
5. Determining the expression patterns, trafficking, and stimulatory requirements
of perforin induction in human CD8+ T cells.
Members of the Betts lab
George Makedonas, Ph.D. McGill University. HIV-specific T cell responses
in HIV acute seroconverters; Perforin expression characteristics in human
CD8+ T cells.
Adam Hersperger (CAMB-MVP, 6/06) B.S. Bucknell University. CMV-specific
T cell responses in HIV-infected individuals; HIV-specific CD8+ T cell function
and HIV viral escape.
Natalie Hutnick (CAMB-GTV, 4/07) B.S. Penn State University. Adenovirus-specific
T cell responses in humans and vaccinated humans and macaques.
Danielle Haney (IGG, 11/07) B.S. Xavier University (New Orleans). TNFa
expression patterns and kinetics in human CD8+ T cells; role of TNFa as a
correlate of immune protection in HIV nonprogression.
Korey Demers (CAMB-MVP, 6/08) B.S. Case Western University
Carolina Pombo-Martinez (CAMB-MVP, 6/08) B.S. Barry University
Jay Gardner Lab Manager; Antibody production and conjugation
Diane Carnathan M.S. University of North Carolina. DNA vaccine-induced
immune responses in mice and rhesus macaques.