Smita Jha, M.D.
Professional Experience
- Director, Calcium & MEN1 Research, Metabolic Diseases Branch, 2020-present
- Assistant Research Physician, Section on Congenital Disorders, NIH Clinical Center, 2018-2020
- Faculty, Inter-Institute Endocrinology Training Program, 2016- present
- Scholar in Translational Research, NIAMS, 2016-2018
- Endocrinology and Metabolism Fellowship, Inter-Institute Endocrinology Training Program, NICHD, 2013-2016
- Internal Medicine Residency, North Shore Medical Center, 2009-2012
- M.D., Bangalore Medical College and Research Institute, 2007
Current Research
Our research aims to elucidate the spectrum, natural history and underlying pathophysiology of disorders of parathyroid function and signaling using natural history studies, translational investigations, and clinical trials to better understand the parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP)/parathyroid hormone receptor type 1 (PTH1R) pathway. We plan to accomplish this by studying unusual disorders of PTH/PTHrP/PTH1R pathway dysregulation as a natural model. The primary disorders of interest include a) Jansen metaphyseal chondrodysplasia, caused by germline variants in PTH1R gene. b) parathyroid cancer caused by neoplastic growth of parathyroid gland with consequent PTH excess c) familial hyperparathyroidism – a heritable predisposition to develop tumors in the parathyroid glands with consequent PTH excess; this includes diseases such as familial hypocalciuric hypercalcemia, multiple endocrine neoplasia type 1 and 4, and hyperparathyroid jaw tumor syndrome, and d) pseudohypoparathyroidism and related disorders of PTH resistance.
Our research led to the identification of germline and somatic inactivating variants in FLCN gene encoding for folliculin as a cause of parathyroid cancer. We also described genotype-phenotype correlation of extra-parathyroid manifestations in patients with hyperparathyroidism-jaw tumor syndrome, the most common heritable cause of parathyroid cancer. More recently, we performed comprehensive phenotyping in patients with Jansen metaphyseal chondrodysplasia – reporting on a distinct facial appearance in the disease and increased predisposition to hearing loss, optic neuropathy, craniosynostosis, dentoskeletal malocclusion and airway compromise.
Applying our Research
Defining the spectrum and natural history of these rare parathyroid disorders will improve our understanding of PTH- and PTHrP-dependent roles in human physiology and disease. We aim to identify druggable targets for treatment of these disorders which lack an effective therapy. Furthermore, enhanced understanding of PTH/PTHrP/PTH1R pathway is likely to have implications in the management of common diseases such as osteoporosis and mineral-bone disorder seen in patients with chronic kidney disease.
Select Publications
- Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.
- Fahrmann JF, Wasylishen AR, Pieterman CRC, Irajizad E, Vykoukal J, Wu R, Dennison JB, Peterson CB, Zhao H, Do KA, Halperin DM, Agarwal SK, Blau JE, Jha S, Rivero JD, Nilubol N, Walter MF, Welch JM, Weinstein LS, Vriens MR, van Leeuwaarde RS, van Treijen MJC, Valk GD, Perrier ND, Hanash SM, Katayama H.
- J Clin Endocrinol Metab (2023 Nov 17) 108:3260-3271. Abstract/Full Text
- Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome.
- Tora R, Welch J, Sun J, Agarwal SK, Bell DA, Merino M, Weinstein LS, Simonds WF, Jha S.
- J Clin Endocrinol Metab (2023 Nov 17) 108:3165-3177. Abstract/Full Text
Research in Plain Language
We study patients with unusual disorders of parathyroid function or signaling. Some examples of these disorders are
- Jansen metaphyseal chondrodysplasia
- parathyroid cancer
- familial hyperparathyroidism like multiple endocrine neoplasia type 1 and 4, familial hypocalciuric hypercalcemia and hyperparathyroidism-jaw tumor syndrome
- pseudohypoparathyroidism and related disorders
We wish to identify biomarkers to predict the disease course and druggable targets to improve the treatment of these disorders.