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Faculty Bijay Mukherji
Professor of Medicine
mukherji@nso2.uchc.edu
Areas of Interest:
The understanding of the basic mechanisms involved in cellular immune
response against human cancer is the major goal of Dr. Mukherji’s
laboratory. Cytolytic T lymphocyte response, the specificity of
response, the role of professional antigen-presenting cells and
mechanisms of peripheral regulation are studied using T cell lines and
various T cell determined peptide epitopes. The studies are carried out
in autologous human tumor systems as the model. More specifically, the
interest of Dr. Mukherji’s laboratory centers around the question of how
T cells that are capable of recognizing peptide epitopes on cancer cells
but exist in an unresponsive state can be reactivated. In this context,
the development of an antigen presentation system capable of activating
and amplifying tumor specific cytolytic T lymphocytes is sought by
putting professional antigen-presenting cells in the center of the
schema. Several cell biological and molecular biological approaches are
studied with the goal of engineering professional antigen-presenting
cells that will provide the requisite signals for activating the
relevant T cell populations. Along with in vitro studies, in
vivo translation studies are also carried out with well-defined
patient population.
Lab Rotation Projects:
Our major interest centers around the question of how to orchestrate a
robust and long-lived cytolytic T cell (CTL) response to tumor
associated epitope in human models. Since CTLs are prone to undergoing
programmed cell death (PCD) as well as activation induced cell death (AICD),
we are probing the molecular mechanism underlying PCD and AICD. We have
found that caspases are not involved in the AICD of CTLs. They die via a
mitochondria-based process that is caspase-independent. it seems that
the death is quite likely mediated by single stranded DNA breaks induced
by the pro-apoptotic protein,apoptosis inducing factor (AIF) released
from mitochondrial dysregulation. Our work suggests that JNK is a player
in themitochondrial release of AIF which then translocates to teh
nucleus where it causes ssDNA breaks. Our present goals are to probe
this pathway in further details and to find points of possible
interdiction so as to keep the CTLs alive longer.
Our other interest is on the subject of peripheral regulation of CTL
activation. Specifically, we wish to figure out which CD4+ T regulatory
cells (natural Tregs or induced Tregs) are the major constraints in
generating tumor epitope specific CTLs. We have recently found that
contrary to the popular belief that natural Treg cells control tumor
immunity, the generation of tumor epitope specific CTLs is not usually
affected by CD4+CD25+ (nTreg cells) but by a regulatory population that
is induced from CD4+CD25- precursors. We are interested in understanding
the mechanism underlying the generation of these types of induced Treg
cells.
Publications
Selected Publications:
Schumacher L, Ribas A, Dissette VB, McBride WH, Mukherji B, Economou
JS, Butterfield LH. Human dendritic cell maturation by adenovirus
transduction enhances tumor antigen-specific T-cell responses. J
Immunother. 2004 May-Jun;27(3):191-200.
Mehrotra S, Stevens R, Zengou R, Chakraborty NG, Butterfield LH,
Economou JS, Dorsky DI, Mukherji B. Regulation of melanoma epitope-specific
cytolytic T lymphocyte response by immature and activated dendritic
cells, in vitro. Cancer Res. 2003 Sep 1;63(17):5607-14.
Butterfield LH, Ribas A, Dissette VB, Amarnani SN, Vu HT, Oseguera D,
Wang HJ, Elashoff RM, McBride WH, Mukherji B, Cochran AJ, Glaspy JA,
Economou JS. Determinant spreading associated with clinical response in
dendritic cell-based
immunotherapy for malignant melanoma. Clin Cancer Res. 2003
Mar;9(3):998-1008.
Schuman JS, Massicotte EC, Connolly S, Hertzmark E, Mukherji B, Kunen
MZ. Increased intraocular pressure and visual field defects in high
resistance wind instrument players. Ophthalmology. 2000
Jan;107(1):127-33.
Chakraborty A, Li L, Chakraborty NG, Mukherji B. Stimulatory and
inhibitory differentiation of human myeloid dendritic cells. Clin
Immunol. 2000 Feb;94(2):88-98.
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