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.
 View more publications, see
Pubmed listing. |
