ANNUAL REPORT - Department of Biotechnology

In stem cell research, the studies showed that
inhibition of stress kinases in primitive hematopoietic
cells result in increased proliferation by making them
more responsive to growth conditions. The
mannose binding lectin FRIL was demonstrated to
have stem cell preservation activity. Optimization of
in vitro expression and cryopreservation of
hematopoietic stem cells is another area of interest
at NCCS, whereby the efforts led to the identification
arachidonic acid (Omega6) and its metabolites as
additives that reduced apoptosis in CD34+ cells.
Further, the conditions for enrichment, freezing and
ex vivo expansion of cord blood megakaryocyte and
dendritic cells have been optimized. This has a
potential future application in thrombocytopenia
therapy and dendritic cell tumor therapy. Embryonic
stem cell (ESC) systems, which have the unique
property to differentiate into all cell types, are being
used to understand developmental events during
neuro- and cardiomyogenesis. The differentiation of
mouse ESCs into neurons, in particular the
dopaminergic neurons, has been achieved. The
studies also indicated that retinoic acid has a role in
increasing the neural progenitor population and
further investigation on a potential role of Wnt
signaling in cardiomyogenesis is underway.
Diabetes
Ongoing studies indicate that insulin protects
cardiomyocytes from oxidative and nitrative stressinduced
apoptosis by inhibiting reactive oxygen and
reactive nitrogen species generation. Similarly,
curcumin pretreatment was found to protect islets
against streptozotocin and cytokine induced damage
through scavenging cellular ROS and augmenting
cellular defense responses. These findings indicate
a therapeutic potential of multiple anti-oxidants on
oxidative and nitrate stress in diabetes. In another
study, for the first time it has been found that chick
pancreatic islets could be used as excellent
alternative in vitro model for physiological and
pharmacological studies in diabetes research.
Cancer Biology
In the area of ovarian tumor stem cells, a distinctive
nuclear-mitochondrial mutational profile and varying
stem cell dynamics has been identified to be
associated with the emergence of a specific lineage
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on a trajectory towards tumorigenesis. The human
homologue of the mouse melanoma gene (M3TR)
was shown to be involved in induction and
maintenance of stemness; its functioning as
microRNA also triggers off a cascade of events that
culminate in cellular transformation. Further, the
deciphering of TNF- mediated signaling pathway(s)
in monolayer and spheroids generated from gliomas
revealed that while the two Cyclin dependent kinase
(CDK) inhibitors p21 cip/waf1 and p27 kip1 are both
expressed on stimulus with TNF-, only p27 might be
important in growth arrest in the spheroids. Towards
exploring the sensitivity of HPV E6 positive cancer
cells to chemotherapeutic drugs, studies revealed
that though upregulation of the DNA damageinducible
gene alpha (Gadd45) occurs as a
consequence of apoptotic response to genotoxic
stress, induction of apoptosis is solely dictated by the
nature of stress and cell type. A potential therapeutic
application of the cholesterol depleting agent,
methyl--cyclodextrin (MCD) in combination with
other conventional cytotoxic drugs to facilitate
reduction of drug dosage that offers a better
chemotherapeutic approach with low toxicity is being
evaluated.
Signal Transduction
Studies on prostrate cancer revealed that
osteopontin regulates the cyclooxygenase-2 (COX-
2) - mediated PGE 2 production and MMP-2 activation
by tumor cells, that in turn, mediate tumor
progression and angiogenesis. The data suggested
that blockade of OPN and COX-2 is a promising
therapeutic approach for the inhibition of tumor
progression by suppressing prostate tumor growth
and angiogenesis. Another study regarding
differential membrane dynamics mediated by
various lectins indicated that lectins with similar
carbohydrate specificity evoke different cellular
responses depending on the cell line lineage,
through differential protein-lectin interactions. An
example is that the jacalin lectin exerts reversible
stress on A431 cells through the induction of
phosphorylation of caveolin-1 and p38 but not JNK,
whereas another lectin viz. PNA, which has a very
similar specificity to that of jacalin, did not induce the
same effect. Further studies suggested that jacalin
cytotoxicity is mediated through the caveolin-c-src
p38 pathway and involves an impairment of the