IndianaCTSI HUB

Dr. Shekhar is the director of the Indiana Clinical and Translational Sciences Institute. As the director, he leads the effort to promote research infrastructure that will accelerate translating new ideas and discoveries into novel therapies and best practices across Indiana. His own research focuses on understanding basic neuroscience mechanisms that could lead into potential clinical applications to treat neuropsychiatric disorders such as panic disorder, schizophrenia, and autism. He conducts numerous NIH funded studies in neuropscyhiatric disorders as well as foundation supported studies, including being the principal investigator of the longitudinal study of disease risk factors in Indiana population.

Broadly speaking, Dr. Shekhar’s research interests are a) neurobiological mechanisms underlying panic, anxiety and fear responses at the basic sciences level; b) clinical program in anxiety disorders that studies a broad range of issues from neuroimaging and etiology to treatment outcomes; c) novel therapeutic approaches to treating severe neuropsychiatric disorders such as schizophrenia; d) mechanisms of abnormal social behaviors in disorders sucj neurofibromatosis, autism spectrum disorders and social anxiety; e)novel methods to discover and rapidly test new drug therapies for neuropsychiatric disorders through translational sicnces. For example, his basic science studies have focused on delineating the neural circuitry involved in panic like responses funded by NIMH, NIH. This recently resulted in the discovery that abnormality in a new chemical called orexin was critical in the development of panic attacks and could lead to new therapies for this disorder. Several potential rodent model of number of anxiety disorders have also been developed in laboratory. His clinical research has developed several novel approaches to treating neuropsychiatric disorders. For example, his recent work demonstrated that selective muscarinic cholinergic agonists could be a completely novel and effective way to treat patients with schizophrenia.

1. Shekhar A, Potter WZ, Lightfoot J, Lienemann J, Dubé S, Mallinckrodt C, Bymaster FP, McKinzie DL, Felder CC. Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia. Am J Psychiatry. 2008 Aug;165(8):1033-9. Epub 2008 Jul 1. PubMed PMID: 18593778.

2. Goddard AW, Ball SG, Martinez J, Robinson MJ, Yang CR, Russell JM, Shekhar A. Current perspectives of the roles of the central norepinephrine system in anxiety and depression. Depress Anxiety. 2010 Apr;27(4):339-50. PubMed PMID: 19960531.

3. Bolbecker AR, Hetrick WP, Johannesen JK, O’Donnell BF, Steinmetz JE, Shekhar A. Secretin effects on cerebellar-dependent motor learning in schizophrenia. Am J Psychiatry. 2009 Apr;166(4):460-6. PubMed PMID: 19223439.

4. Truitt WA, Johnson PL, Dietrich AD, Fitz SD, Shekhar A. Anxiety-like behavior is modulated by a discrete subpopulation of interneurons in the basolateral amygdala. Neuroscience. 2009 May 5;160(2):284-94. PubMed PMID: 19258024; PubMed Central PMCID: PMC2682359.

5. Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S, Träskman-Bendz L, Goddard AW, Brundin L, Shekhar A. A key role for orexin in panic anxiety. Nature Med. 2010 Jan;16(1):111-5. PubMed PMID: 20037593; PubMed Central PMCID: PMC2832844.

6. Chambers RA, Sentir AM, Conroy SK, Truitt WA, Shekhar A. Cortical-striatal integration of cocaine history and prefrontal dysfunction in animal modeling of dual diagnosis. Biol Psychiatry. 2010 Apr 15;67(8):788-92. PubMed PMID: 19880093; PubMed Central PMCID: PMC2849854.

7. Molosh AI, Johnson PL, Fitz SD, Dimicco JA, Herman JP, Shekhar A. Changes in central sodium and not osmolarity or lactate induce panic-like responses in a model of panic disorder. Neuropsychopharmacology. 2010 May;35(6):1333-47. PubMed PMID: 20130534.

8. H Le-Niculescu, Y Balaraman, S D Patel, M Ayalew, J Gupta, R Kuczenski, A Shekhar, N Schork, M A Geyer & A B Niculescu. Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms Translational Psychiatry (2011) 1, e9; doi:10.1038/tp.2011.9 Published online 24 May 201i

9. JM Brittain, DB Duarte, SM. Wilson, W Zhu, C Ballard, PL Johnson, N Liu, W Xiong, MS Ripsch, Y Wang, JC Fehrenbacher, SD Fitz, M Khanna, C-K Park, BS Schmutzler, BM Cheon, MR Due, T Brustovetsky, NM Ashpole, A Hudmon SO Meroueh, CM Hingtgen, N Brustovetsky, R-R Ji, JH Hurley, X Jin, A Shekhar, X-M Xu, GS Oxford, MR Vasko, FA. White, and R Khanna. Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca2+ channel complex. Nature Med. 2011; 17(7):822-9.

1. R01 MH52619 -09 (Anantha Shekhar) Dates: 05/1/07 – 06/01/12 Role: PI NIH; NIMH Title: Neurobiology of Panic and Anxiety Disorders Study the role of dorsomedial hypothalamus (DMH) in the development of panic disorder. Study GABA- glutamate interactions; the afferent and efferent pathways; and the role of orexin.

2. R01 MH65702-04 (Anantha Shekhar) Dates: 7/1/09 – 6/30/14 Role: PI NIH; NIMH Title: Role of Serotonin and CRF Pathways in Anxiety and HPA Regulations Study the role of serotonin and CRF pathways in regulating anxiety and stress responses. We are specifically studying the interaction with a select group of serotonin neurons in raphe and the limbic pathways

3. R01 MH52619 -11S1 (Anantha Shekhar) Dates: 05/1/09 – 06/01/12 Role: PI NIH; NIMH Title: Neurobiology of Panic and Anxiety Disorders This is supplement to study developmental Study the role of gene changes during pre-adolescence and adolescence in the development of panic disorder.

4. UL1RR025761-01 (Anantha Shekhar) Dates: 05/1/08 – 4/30/13. Role: PI NIH; NCRR Title: Indiana Clinical and Translational Sciences Institute To establish a new institute that facilitates clinical and translational biomedical research across the state of Indiana. This is an institute established by the CTSA to Indiana and Purdue Universities

5. KL2RR025760-01 (Anantha Shekhar) Dates: 05/1/08 – 4/30/13. Role: PI NIH; NCRR Title: Indiana Clinical and Translational Sciences Institute – K12 Program To establish a new training and career development program providing mentoring programs and individual K08, K23, and K30 equivalent awards to junior investigators in clinical and translational biomedical research within the Indiana CTSI.

6. TL1RR025759-01 (Anantha Shekhar) Dates: 05/1/08 – 4/30/13. Role: PI NIH; NCRR Title: Indiana Clinical and Translational Sciences Institute – T32 Program To establish a new training program providing mentoring programs and individual training fellowships to pre- and post-doctoral candidates in clinical and translational research programs within the Indiana CTSI.