# Identification of pathways involved in orbital adipogenesis using functional genomics

> **NIH NIH K08** · JOHNS HOPKINS UNIVERSITY · 2020 · $172,441

## Abstract

“Identification of pathways involved in orbital adipogenesis using functional genomics”
Project Summary/Abstract
Graves disease, the most common orbital inflammatory disease, causes significant
disfigurement, decreased quality of life, and ocular morbidity, including blindness. Although the
pathophysiology of Graves disease is not entirely understood, it is thought that an immune
response to auto-antigens expressed on thyrocytes and orbital fibroblasts, the thyroid
stimulating hormone receptor and the insulin-like growth factor-1 receptor, induce a series of
inflammatory cytokine cascades that result in orbital soft tissue expansion through fibrosis and
adipogenesis.1-8 Current treatment approaches focus on symptom control, anti-inflammatory
medications, and surgical rehabilitation of patients, and do not target underlying disease
mechanisms. Currently, research is underway to develop and test agents that target cytokines
or auto-antigens to blunt the immune response.9 However, little research has been devoted to
understand the mechanisms of orbital adipogenesis, one of the final common pathways of the
inflammatory cascades causing orbital soft tissue expansion. This is especially important as
orbital adipogenesis likely differs from other adipose tissue depots in the body based on the
alternate embryologic origins of orbital fat.
I propose a plan for multiple years of training as a clinician-scientist working to identify the
molecular pathways involved in orbital adipogenesis in Graves disease that may serve as
potential therapeutic targets. Specifically, I will focus on non-coding RNAs (ncRNAs), which
have been shown to regulate differentiation in multiple systems and have tissue-specific
expression and function in different adipose depots in mice.10 Understanding the basis of
ncRNA function in orbital adipogenesis may provide potential therapeutic targets. I will work
under the mentorship of senior investigators whose diverse areas of expertise will be critical in
my training. The team of mentors who will work with me are productive NIH-funded scientists
who have made valuable contributions to their respective fields. I will train in the laboratory of
Dr. Seth Blackshaw, Director of the Center for High Throughput Biology, learning techniques of
functional genomics that he has applied to the study of neurogenesis in the hypothalamus and
retina. With the guidance of Dr. William Wong of the Center for Metabolism and Obesity
Research, who has expertise in adipocyte biology, I will apply the techniques used in the
Blackshaw lab to the study of orbital adipogenesis. Dr. Terry Smith of the Departments of
Medicine and Ophthalmology at University of Michigan, an expert in inflammatory signaling in
orbital fibroblasts in Graves disease, will serve as a mentor by focusing my education on
cytokine signaling and adipogenesis to Graves disease. Using the combined expertise of these
mentors, I will learn how to design experiments that will identify transcrip...

## Key facts

- **NIH application ID:** 10004056
- **Project number:** 5K08EY027093-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Fatemeh Rajaii
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $172,441
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004056

## Citation

> US National Institutes of Health, RePORTER application 10004056, Identification of pathways involved in orbital adipogenesis using functional genomics (5K08EY027093-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10004056. Licensed CC0.

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