Aug
12
Mon
2013
Invited Talk: Epigenetic Changes due to DNA Methylation in Human Epithelial Tumors @ Acharya Hall
Aug 12 @ 12:18 pm – 12:39 pm

sathyaK. Satyamoorthy, Ph.D.
Director, Life Sciences Centre, Manipal University, India


Epigenetic Changes due to DNA Methylation in Human Epithelial Tumors

Extensive global hypomethylation in the genome and hypermthylation of selective tumor specific suppressor genes appears to be a hallmark of human cancers.  Data suggests that hypermethylation of promoter region in genes is more closely related to subsequent gene expression; contrary to gene-body DNA methylation.  The intricate balance between these two may contribute to the progressive process of development, differentiation and carcinogenesis.  Epigenetic changes encompass, apart from DNA methylation, chromatin modifications through post-translational changes in histones and control by miRNAs.  At the genome level, effects from these are compounded by copy number variations (CNVs) which may ultimately influence protein functions.    From clinical perspective, changes in DNA methylation occur very early which are reversible and are influenced by environmental factors.  Therefore, these can be potential resource for identifying therapeutic targets as well as biomarkers for early screening of cancer.  Our current efforts in profiling genome wide DNA methylation changes in oral, cervical and breast cancers through DNA methylation microarray analysis has revealed number of alterations critical for survival, progression and metastatic behavior of tumors.  Bioinformatics and functional analysis revealed several key regulatory molecules controlled by DNA methylation and suggests that DNA methylation changes in several CpG islands appear to co-segregate in the regions of miRNAs as well as in the CNVs.  We have validated the signatures for methylation of CpG islands through bisufite sequencing for essential genes in clinical samples and have undertaken transcriptional and functional analysis in tumor cell lines.    These results will be presented.

Aug
13
Tue
2013
Plenary Address: Making sense of pathogen sensors of Innate Immunity: Utility of their ligands as antiviral agens and adjuvants for vaccines. @ Acharya Hall
Aug 13 @ 9:17 am – 9:55 am

SuryaprakashSuryaprakash Sambhara, DVM, Ph.D
Chief, Immunology Section, Influenza Division, CDC, Atlanta, USA


Making sense of pathogen sensors of Innate Immunity: Utility of their ligands as antiviral agents and adjuvants for vaccines.

Currently used antiviral agents act by inhibiting viral entry, replication, or release of viral progeny.  However, recent emergence of drug-resistant viruses has become a major public health concern as it is limiting our ability to prevent and treat viral diseases.  Furthermore, very few antiviral agents with novel modes of action are currently in development.  It is well established that the innate immune system is the first line of defense against invading pathogens.  The recognition of diverse pathogen-associated molecular patterns (PAMPs) is accomplished by several classes of pattern recognition receptors (PRRs) and the ligand/receptor interactions trigger an effective innate antiviral response.  In the past several years, remarkable progress has been made towards understanding both the structural and functional nature of PAMPs and PRRs.  As a result of their indispensable role in virus infection, these ligands have become potential pharmacological agents against viral infections.  Since their pathways of action are evolutionarily conserved, the likelihood of viruses developing resistance to PRR activation is diminished.  I will discuss the recent developments investigating the potential utility of the ligands of innate immune receptors as antiviral agents and molecular adjuvants for vaccines.

Suryaprakash (1) Suryaprakash (4) Suryaprakash-Nagaraja

Plenary Talk: Biosensor and Single Cell Manipulation using Nanopipettes @ Amriteshwari Hall
Aug 13 @ 10:06 am – 10:49 am

NaderNader Pourmand, Ph.D.
Director, UCSC Genome Technology Center,University of California, Santa Cruz


Biosensor and Single Cell Manipulation using Nanopipettes

Approaching sub-cellular biological problems from an engineering perspective begs for the incorporation of electronic readouts. With their high sensitivity and low invasiveness, nanotechnology-based tools hold great promise for biochemical sensing and single-cell manipulation. During my talk I will discuss the incorporation of electrical measurements into nanopipette technology and present results showing the rapid and reversible response of these subcellular sensors  to different analytes such as antigens, ions and carbohydrates. In addition, I will present the development of a single-cell manipulation platform that uses a nanopipette in a scanning ion-conductive microscopy technique. We use this newly developed technology to position the nanopipette with nanoscale precision, and to inject and/or aspirate a minute amount of material to and from individual cells or organelle without comprising cell viability. Furthermore, if time permits, I will show our strategy for a new, single-cell DNA/ RNA sequencing technology that will potentially use nanopipette technology to analyze the minute amount of aspirated cellular material.

Invited Talk: The system of PAS proteins (HIF and AhR) as an interface between environment and skin homeostasis @ Acharya Hall
Aug 13 @ 2:33 pm – 2:50 pm

andreyAndrey Panteleyev, Ph.D.
Vice Chair, Division of Molecular Biology, NBICS Centre-Kurchatov Institute, Moscow, Russia


The system of PAS proteins (HIF and AhR) as an interface between environment and skin homeostasis

Regulation of normal skin functions as well as etiology of many skin diseases are both tightly linked to the environmental impact. Nevertheless, molecular aspects of skin-environment communication and mechanisms coordinating skin response to a plurality of environmental stressors remain poorly understood.

Our studies along with the work of other groups have identified the family of PAS dimeric transcription factors as an essential sensory and regulatory component of communication between skin and the environment. This protein family comprises a number of hypoxia-induced factors (HIF-alpha proteins), aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT), and several proteins implicated in control of rhythmic processes (Clock, Period, and Bmal proteins). Together, various PAS proteins (and first of all ARNT – as the central dimerization partner in the family) control such pivotal aspects of cell physiology as drug/xenobiotic metabolism, hypoxic and UV light response, ROS activity, pathogen defense, overall energy balance and breathing pathways.

In his presentation Dr. Panteleyev will focus on the role of ARNT activity and local hypoxia in control of keratinocyte differentiation and cornification. His recent work revealed that ARNT negatively regulates expression of late differentiation genes through modulation of amphiregulin expression and downstream alterations in activity of EGFR pathway. All these effects are highly dependent on epigenetic mechanisms such as histone deacetylation. Characterisation of hypoxia as a key microenvironmental factor in the skin and the role of HIF pathway in control of dermal vasculature and epidermal functions is another major focus of Dr. Panteleyev’s presentation.

In general, the studies of Dr. Panteleyev’s laboratory provide an insight into the PAS-dependent maintenance of skin homeostasis and point to the potential role of these proteins in pathogenesis of environmentally-modulated skin diseases such as barrier defects, desquamation abnormalities, psoriasis, etc.