# Hepatoprotective Mechanisms of TTC39B Deficiency

> **NIH NIH K01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $153,652

## Abstract

Hepatoprotective Mechanisms of TTC39B Deficiency PI: Hsieh, Joanne
Project Summary/Abstract
This K01 application is designed to provide the necessary resources and training to transition
Dr. Joanne Hsieh to full independence in the field of lipid metabolism in liver disease. The
proposed work and training will be performed at Columbia University Medical Center (CUMC) in
the Department of Medicine, which has demonstrated a commitment to junior faculty
mentorship. She will be mentored by Dr. Alan Tall, who is a pre-eminent investigator in
lipoprotein metabolism and atherosclerosis. With Dr. Joel Lavine in the Department of Pediatrics
as her co-mentor, Dr. Hsieh will transition her focus towards non-alcoholic fatty liver disease
(NAFLD). Dr. Lavine has an extensive record of clinical research in adult and pediatric NAFLD,
and will be integral in Dr. Hsieh's training in building translational aims into her
biomechanistically-focused research. Dr. Hsieh will continue her research on TTC39B, a novel
gene significantly associated with HDL-cholesterol in human GWAS. Dr. Hsieh recently showed
that deficiency in TTC39B conferred a dramatic protection from steatohepatitis in mice. This
hepatoprotection was associated with inhibited sterol-regulatory element binding protein-1
(SREBP-1) activation and decreased lipogenic gene expression. The overall goal of the
proposal to determine how decreased expression of specific lipogenic genes contributes the
hepatoprotective effects of TTC39B deficiency. Dr. Hsieh will conduct the investigations in a
diet-induced mouse model of steatohepatitis that exhibits many of the histological features
observed in human NASH, including inflammatory cell infiltration and fibrosis. In the first aim,
TTC39B's effect on SREBP-1 activation will be further explored mechanistically to understand
the early pathogenesis of NAFLD. The first subaim will determine whether the SREBP-1
inactivation in TTC39B deficiency is driving the protection from steatohepatitis, while the second
will investigate the role of phospholipid metabolism in this inactivation. The second aim will
explore whether the suppression of phosphatidic acid signalling in TTC39B deficiency prevents
the progression of NAFLD to the more severe non-alcoholic steatohepatitis (NASH). Dr. Hsieh's
scientific research and career development will be further supported by members of her
advisory board, including Dr. Muredach Reilly, Dr. Robert Schwabe, and Dr. Richard
Deckelbaum. The mentoring and advisory team will help broaden Dr. Hsieh's approach to
scientific hypothesis-testing and ensure her success as an independent investigator.

## Key facts

- **NIH application ID:** 10407976
- **Project number:** 5K01DK114380-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joanne Hsieh
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $153,652
- **Award type:** 5
- **Project period:** 2018-07-05 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10407976

## Citation

> US National Institutes of Health, RePORTER application 10407976, Hepatoprotective Mechanisms of TTC39B Deficiency (5K01DK114380-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10407976. Licensed CC0.

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