Current Research:

Currently I work at Allen Discovery Center at Tufts University under the directorship of Dr. Michael Levin. The Allen Center integrates molecular physiology, cell biology, developmental genetics, biophysics, computer science, and engineering to understand the storage and processing of information in living tissues. Hence, it provides an excellent environment for all round development of research and collaborations.

I study bioelectrical signals (endogenous ion fluxes and membrane voltage patterns) that make up part of the language used by cells to fulfill complex patterning and organizational needs of the host organism. These natural voltage patterns exists in all cells and I use a convergence of variety of genetic, biophysical and molecular physiology to develop new tools to track and manipulate these bioelectric conversations between cells and tissues.

My work focuses on understanding and learning to utilize the bioelectrical control systems regulating cell proliferation and differentiation towards formation of 3-dimentional organ structures. The effort is to understand bioelectric information processing during embryo development and learn to control it to achieve regeneration of tissues and organs as well as normalize neoplastic growth. Proof-of-principle experiments have demonstrated the incredible potential of biophysical signals in regulating organ development and regeneration in adults. Work includes development of new techniques for rational manipulation of ion flows, voltage gradients and electric fields. Applications of this have been demonstrated in induction of whole eye tissues, and brain tissues.

The continued current effort is towards understanding the spatial information (3-D shape and structure) and temporal information (signal patterns that carry information) detected, remembered and processed by the cells and tissues towards formation of organs like the nervous system and similar such information processing in non-neural organs like heart. Projects also include development, regeneration and plasticity of brain information and somatic information.

I use a convergence of molecular biophysics and computational modeling to understand how this occurs at multiple levels of organization. Further applications of this work are in research and development of ionoceuticals (drugs targeting ion channels), biomedical engineering, synthetic biology, and robotics.

Ph.D.

My graduate work under the supervision of Dr. Nelson D. Horseman, focused on studying biophysical forces during mammary gland (breast) development with emphasis on the discovery of serotonin system, its influence on the biophysical forces and disease development.

My contributions were in 5 specific subareas:

1. Development and Characterization of an In Vitro Model of Differentiated Human Mammary Epithelium. – I developed and characterized the a model of differentiated human mammary epithelium. My model possesses properties of multipotent progenitor cells as evidenced by differentiation into both the basal and milk secreting luminal cells

2. Discovery of Serotonin System Components in the Mammary Epithelium and how they Regulate milk synthesis and secretion via regulating Transepithelial Resistance. – My study showed a change in serotonin levels (increase by 250%) within the mammary gland during lactation (milk synthesis). I discovered the components of mammary serotonin system; (receptor, transporter and their localization), within the mammary epithelium. My work is the first to show that serotonin directly regulates mammary transepithelial resistance in human and mouse.

3. Discovery of Serotonin Signaling Mechanism via 5-HT7 Receptor and the Dynamic Regulation of Mammary Epithelial Tight Junctions. – I discovered the biphasic regulation of breast transepithelial resistance by serotonin which is essential for regulation of milk secretion and initiation of involution. I uncovered a phenomenon of a switch in serotonin receptor 7 signaling based on extent of serotonin exposure.

4. Discovery of Serotonin Physiology and its influences in Human Breast Cancers. – My work is the first account illustrating direct involvement of serotonin in breast cancers. My work showed that increased serotonin biosynthetic capacity accompanied by multiple changes in the serotonin receptor expression and signaling favor malignant progression of human breast cancers.

5. Discovery of Epithelial Regeneration Responses to Serotonin during Epithelial Homeostasis. – The time of exposure of the epithelium to serotonin affects its regenerative capacity, first through induction of cell shedding and then through induction of cell death, shifting the balance from functional regenerative epithelium to a regressing epithelium.

In summary, my research work has been along an interdisciplinary path, with contributions to the fields of integrative organ/systems biology, physiology, biophysics, and cancer biology.