# Activity-Dependent Regulation of the Neuronal Epigenome

> **NIH NIH K08** · HARVARD MEDICAL SCHOOL · 2020 · $196,085

## Abstract

This K08 proposal describes a four-year research and training plan that will facilitate the transition of Dr. Brian
Kalish to an independent academic researcher in the field of neuronal chromatin biology. Dr. Kalish has a
strong background in basic research and recently completed post-graduate training in neonatal-perinatal
medicine. Dr. Kalish is interested in the molecular mechanisms underlying neurodevelopmental disorders, and
in using insights from these disorders to better understand normal brain development. To this end, Dr. Kalish
has identified a novel activity-dependent post-translational switch on a histone lysine methyltransferase,
SETD2, that regulates its interactome and function. The overarching aim of this proposal is to obtain a more
comprehensive understanding of the activity-dependent regulation of the epigenome by elucidating the
molecular mechanisms underlying the function of SETD2 in the brain. SETD2 is strongly implicated in
intellectual disability and autism, and therefore represents an ideal candidate through which to link
pathophysiological changes characteristic of neurodevelopmental disorders to defined alterations in gene
expression and chromatin structure. The candidate proposes three specific aims: 1. Characterize the temporal
and stimulus-specific dynamics of neuronal activity-dependent SETD2 phosphorylation; 2. Investigate how
activity-dependent phosphorylation of SETD2 disrupts interaction with a chromatin-remodeling complex; and 3.
Study the role of SETD2 phosphorylation in activity-dependent transcription and alternative splicing using a
novel SETD2 phospho-mutant mouse. This research has significance, as knowledge gained from this study will
impact our understanding of epigenetic regulation in the brain, as well as our knowledge of
neurodevelopmental disorders. Dr. Kalish will receive mentorship from his scholarship oversight committee
composed of distinguished scientists with expertise related to key areas of this proposal. The training
opportunities and resources at Harvard Medical School are an ideal environment for the candidate’s career
development program. The candidate’s mentor, Dr. Michael Greenberg, is a NIH funded neurobiologist with a
track record of successful mentorship. A detailed career development and training plan is presented that
includes mentored research, didactic coursework, self-directed readings, seminars, and presentations at
scientific meetings. The candidate details a timeline for completion of the research aims, preparation of
manuscripts, and a future R01 application. The expertise and knowledge gained from this K08 will enable Dr.
Kalish to obtain R01 funding to launch an independent research career focused on the regulation of the
epigenome in brain development and disorders.

## Key facts

- **NIH application ID:** 9970916
- **Project number:** 1K08NS112338-01A1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Brian Kalish
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,085
- **Award type:** 1
- **Project period:** 2020-04-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970916

## Citation

> US National Institutes of Health, RePORTER application 9970916, Activity-Dependent Regulation of the Neuronal Epigenome (1K08NS112338-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9970916. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*