Defective skeletal patterning is a major contributor of congenital limb malformations, which are among the most frequent birth defects in humans. Loss of epigenetic regulation has been associated with several debilitating human disorders including immune and neurodevelopmental disorders among others. Aberrant DNA modifications either due to mutations in enzymes that catalyze the establishment, maintenance or the readers of these marks are intricately associated with human developmental disorders. Building on Dr. Kota?s previous training and experience in the fields of epigenetic regulation of monoallelic gene expression and stem cell biology, this K01 application will support advanced research training in the interdisciplinary areas of developmental skeletal biology and epigenomics which will enable him to become an independent investigator in the emerging multidisciplinary area of epigenetic regulation of developmental skeletal biology. Specifically, during the K01 award period, Dr. Kota will receive advanced training in 1) theoretical and practical aspects of skeletal development and homeostasis, 2) analysis of mouse models of skeletal disorders and 3) genomic analysis of early limb progenitor cells, from a team of mentors at Harvard University. Training will be completed via formal coursework, hands-on lab training, mentored research and regular attendance at seminars and workshops. Based on the PI's preliminary findings in the mice, the research will focus on elucidating the role of the epigenetic gene regulation during skeletal patterning and aims to evaluate the transcriptome, epigenetic modifications in skeletal progenitors. In summary, the overall goal of the proposal is to understand the epigenetic regulation and its key targets during embryonic skeletal development to get better insights into human congenital limb abnormalities that eventually will lead to better therapeutic avenues.

Public Health Relevance

Congenital limb malformations (CLM) and craniofacial deformities are among the most frequent malformations in humans that often require extensive surgeries and have significant bearing on affected individuals and their families. This multidisciplinary project focuses to understand epigenetic transitions during normal skeletal patterning and will uncover the molecular basis through which genetic deficiency in an epigenetic regulator results in defects in limbs and digits. In addition, the Principal Investigato of this proposal will receive collective advanced training in the areas of developmental skeletal biology, epigenomic analysis and bioinformatics to strengthen his multidisciplinary expertise essential to execute the proposed specific aims.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AR069197-03
Application #
9435086
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Chen, Faye H
Project Start
2016-03-14
Project End
2021-02-28
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Kota, Satya K; Kota, Savithri B (2017) Noncoding RNA and epigenetic gene regulation in renal diseases. Drug Discov Today 22:1112-1122