Deepak Nihalani

faculty photo
Research Assistant Professor of Medicine
Department: Medicine

Contact information
Renal-Electrolyte and Hypertension Division
405 CRB
415 Curie Blvd
Philadelphia, PA 19104
Office: 215-898-0192
Fax: 215-898-0189
Education:
BS (Microbiology)
Delhi University, India, 1990.
MSc (Microbiology)
Delhi University, India, 1992.
PhD (Biotechnology)
Panjab University, Chandigarh, India, 1997.
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Description of Itmat Expertise

Glomerular Diseases that affect kidney function such as diabetes and hypertension are major causes of ESRD (end stage renal disease) in the United States. Glomerular dysfunction leading to proteinuria and loss of kidney function is major cause of morbidity and mortality among kidney patients. Therefore, studies aimed at understanding the molecular events leading to proteinuria are important in developing therapeutic approaches towards prevention of ESRD. I was quite fascinated by the complexity of the filtration system that is unique in its structural and protein composition. Many studies have now established that podocytes and their specialized junctions commonly known as slit diaphragm are are physical barrier that perform the filtration function of kidney. It has been my long term goal to understand the molecular organization of this filtration assembly of the kidney. The current focus of my lab is to understand the dynamic changes in the slit diaphragm proteins that are induced in response to various glomerular disorders. Many slit diaphragm proteins including Neph1 and Nephrin have been identified that are localized at these junctions suggesting an active role for these proteins and their complexes in molecular events that regulate the integrity of slit diaphragm. My laboratory was the first to identify a novel interaction between Neph1 and the motor protein Myo1c, which we propose is involved in the organization of Neph1 complex during glomerular injury. We utilize modern microscopic, cell culture and animal models to investigate the role of Neph1 and other slit diaphragm proteins in podocyte biology. Our studies provide data on the critical molecular events leading to podocyte effacement and podocyte recovery during an injury/recovery event. Importantly, defining these critical molecular changes and their regulation will reveal novel therapeutic approaches aimed at reducing glomerular injury and improving recovery from a glomerular injury.

Description of Research Expertise

Diseases of the renal glomerulus that result in the nephrotic syndrome are important causes of morbidity and mortality. Injury to the kidney glomerulus is often characterized by heavy proteinurea associated with the loss of kidney filtration barrier commonly referred to as slit diaphragm. Significant progress has been made to discover the proteins localized at the slit diaphragm yet little is known about the spatial arrangement of these proteins and how that contributes to the actual kidney filter. My research aim is to understand the regulation and function of the proteins that are the critical components of this slit diaphragm and how they assemble to form a functional glomerular filtration barrier. Although not proven, it is believed that the slit diaphragm is formed by homophilic and heterophilic interactions between the extracellular domains of various proteins including Nephrin, Neph1, Fat1 and Fat2. Intracellularly, proteins such as ZO-1, CD2AP, Nck, and Grb2 are thought to connect the slit diaphragm membrane proteins Neph1 and Nephrin to the actin microfilaments thereby forming the intracellular signaling network. The focus of my research is to define the intracellular signaling pathways that are activated in response to the activation of Nephrin and Neph1. For this purpose we use a combination of biochemical, molecular biology and systems biology approaches to define the functional regions in these proteins and identify their novel interacting partners. We are also currently engaged in developing animal models including the transgenic and knockout mouse models and the zebrafish models that will be instrumental in examining the functional biology of proteins and their interactions, specifically in the podocytes. My other research interests involve, determining the solution based structures of these slit diaphragm proteins through SAXS (small angle X-ray scattering) analysis and understand their spatial distribution at the slit diaphragm.

Apart form the basic science, my group is also interested in translational science where we have used structure-based rational designing to identify novel molecules that are targeted towards regulating the signaling of slit diaphragm proteins Nephrin and Neph1. This is in line with our recent studies that demonstrate inhibiting signaling of Neph1 is of therapeutic value. Our long term goal is to develop therapeutic alternatives for preventing podocyte loss during injury to a glomerulus. Thus we would like to complement our basic science discoveries with applications in the clinical field.

Selected Publications

Arash Darafsheh, Consuelo Guardiola, Deepak Nihalani, Daeyeon Lee, Jarod C. Finlay, Alejandro Cárabe: Biological super-resolution imaging by using novel microsphere-embedded coverslips. Proc. SPIE 9337 , March 11 2015.

Solanki AK, Rathore YS, Badmalia MD, Dhoke RR, Nath SK, Nihalani D, Ashish: Global shape and ligand binding efficiency of the hiv-1 neutralizing antibodies differs from the ones which cannot neutralize. Journal of Biological Chemistry(M114.563486), December 2014.

George B, Fan Q, Dlugos CP, Soofi AA, Zhang J, Verma R, Park TJ, Wong H, Curran T, Nihalani D, Holzman LB: Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis. Kidney International. Nature Publishing Group, 85(6): 1382-94, June 2014.

Arif E, Rathore YS, Kumari B, Ashish F, Wong HN, Holzman LB, Nihalani D: Slit diaphragm protein Neph1 and its signaling: a novel therapeutic target for protection of podocytes against glomerular injury. Journal of Biological Chemistry 289(14): 9502-18, April 2014.

Deepak Nihalani: Diabetes and Kidney Function. J Diabetes MetabDisord Control 1(2), 2014.

Furcht CM, Rojas AM, Nihalani D, Lazzara MJ: Diminished functional role and altered localization of shp2 in non-small cell lung cancer cells with EGFR-activating mutations. Oncogene doi: 10.1038/onc.2012.240: doi: 10.1038/onc.2012.240, May 2013.

Tiwari A, Jung JJ, Inamdar SM, Nihalani D, Choudhury A: The Myosin Motor Myo1c is Required for VEGFR2 Delivery to the Cell Surface and for Angiogenic Signaling. Am J Physiol Heart Circ Physiol 304(5): H687-96, 2013.

Arif E, Nihalani D: Glomerular filtration barrier assembly. Journal of Postdoctoral Research Page: 33-45, 2013.

Arif E, Kumari B, Wagner MC, Zhou W, Holzman LB, Nihalani D: Myo1c, an Unconventional myosin required for zebrafish glomerular development. Kidney International Page: 1154-65, 2013.

Nihalani D, Susztak K: Sirt1-claudin 1 crosstalk in regulating renal function. Nature Medicine 19(11): 1371-2, 2013.

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Last updated: 06/28/2015
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