Maverick Science mag 2013-14

Mandal, shown with members of his lab, clockwise from top left: Arunoday Bhan, Mandal, Shyam
Prakash, Paromita Deb and Aarti Bashyal.
“As my primary education is in chemistry, I always
wanted to be a chemist,” he said. “However,
as I studied more and more biology, I wondered
more and more how cells function, how life functions,
and how genomes are organized and function.”
Mandal’s research focuses on histone modification,
gene regulation and epigenetics in the human
system. Histones are groups of basic proteins present
in the nuclei of cells that form nucleosomes,
which are sections of DNA that are wrapped tightly
around a core of histones, like spools of thread.
Gene regulation is the process of turning genes
on and off. Early in their development, cells begin
to take on specific functions, and gene regulation
ensures that the right genes are expressed at the
right times. Gene regulation can also help an organism
respond to its environment. It is accomplished
by a variety of mechanisms including
chemically modifying genes and using regulatory
proteins to turn genes on or off.
Epigenetics is the study of external modifications
to DNA that turn genes on or off. These modifications
do not change the DNA sequence, but
they do affect how cells read genes. Epigenetic
changes alter the physical structure of DNA. These
changes are not solely genetic, but are influenced
by environmental stimuli such as hormones and
nutrients.
“My primary research interest is to understand
the epigenetic mechanism of gene expression and
its regulation in humans,” Mandal said. “This area
of research has profound consequences in understanding
the mechanism of gene regulation, chromatin
(a complex of nucleic acids and proteins in
the cell nucleus that condenses to form chromosomes
during cell division) dynamics and various
human diseases including cancer and cardiovascular
diseases.”
Though not even a decade into his career, Mandal
has established a reputation as a top-notch researcher.
He earned a Texas Advanced Research
Program grant in 2006 and since then he has
helped secure over $2 million in funding for projects
with which he’s been involved. In May he was
chosen to receive the College of Science Outstanding
Research Award, given annually to a faculty
member who makes critical contributions to their
field in the area of research.
“Dr. Mandal is a quality teacher and a top-rate
biochemist,” said Rasika Dias, professor and chair
of the chemistry and biochemistry department. “He
is a good team player who collaborates closely with
a wide group of scientists at UT Arlington and
around the world. He has established a world-class
research laboratory to study gene regulation mechanisms
and to develop treatments for diseases resulting
from out of control genes. He is also an
expert on hormone action, such as the effect of estrogen
on breast cancer. We’re proud to have him
as a colleague in our department.”
M
andal’s lab is a busy
place, as he has numerous
research projects
going on at any
given time. One current
project involves
understanding the epigenetics
of cancer biology,
tumor microenvironment and targeted therapy.
In the past six months Mandal and his students
had papers published in the journals
Oncogene and the British Journal of Cancer detailing
their investigation of the epigenetics of tumor
microenvironment in vivo using mice models of
human cancer.
“Understanding the tumor microenvironment
and the signaling mechanism that controls tumor
growth, angiogenesis, and metastasis, is critical for
developing novel and effective cancer therapy,”
Mandal said.
In the Oncogene manuscript, which he co-authored
with former postdoctoral fellow Khairul
Ansari and postdoctoral researcher Sahba Kasiri,
Mandal demonstrated that mixed lineage leukemia
(MLL), a gene which is associated with blood cell
differentiation and leukemia, is closely involved in
vasculogenesis and angiogenesis (mechanisms
which implement the formation of the vascular network
in the embryo). MLL is also a chromatinmodifying
enzyme that controls gene expression
and chromatin dynamics in human cells. His group
also found for the first time that MLL1 is critical for
hypoxia signaling and tumor growth, and that antisense-mediated
targeting of MLL1 results in
tumor growth inhibition in a mice model. Hypoxia
signaling and angiogenesis are major trademarks
that help tumors grow and metastasize. Molecules
that inhibit angiogenesis are potential anti-cancer
drugs.
“Because MLL1 is so crucial to angiogenesis and
tumor cell proliferation, gene targeting to MLL1 resulted
in tumor suppression of tumor growth in
pre-clinical models of human cancer,” Mandal said.
“This is the first time in literature to show that an
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