Institute for Fundamental Biomedical Research

Education

• A.B., Biological Sciences, University of California, Santa Barbara, 1978
• Ph.D., Microbiology, University of California, Los Angeles, 1983

Overview

Dr. Osborne is associate dean for Basic Research and director of the Johns Hopkins All Children's Institute for Fundamental Biomedical Research. He is a professor of medicine in the Division of Endocrinology, Diabetes and Metabolism of the Johns Hopkins University School of Medicine.

Dr. Osborne’s career has been focused on the molecular aspects of gene expression and regulation. Born in Ouray, Colorado, he studied fundamental biochemistry and molecular biology at the University of California, Santa Barbara and then earned his Ph.D. in microbiology and molecular biology at UCLA. As a graduate student, he worked on gene regulation in human adenoviruses with Arnold Berk, M.D., at UCLA and was one of the first to construct adenovirus recombinant viruses and analyze their expression in cultured cells. His studies were among the first to show that an AT rich “TATA” sequence was essential for normal RNA pol II gene expression in eukaryotic cells. His studies analyzed this in the normal physiological context of the adenovirus genome, which could not be done for host encoded genes at that time.

He continued his interest in the regulation of gene expression through postdoctoral training at the University of Texas Southwestern Medical Center, where he became an assistant professor, working in the lab of Michael Brown, M.D., and Joseph Goldstein, M.D., who won the 1985 Nobel Prize in Physiology or Medicine “for their discoveries concerning the regulation of cholesterol metabolism.” It was during this time that he began a career-long interest in the connection between metabolism and gene regulation, which has been the underlying theme of his research focus to the present day.

Dr. Osborne spent 20 years at UC Irvine, working his way up to full professor and chairman of the Department of Molecular Biology and Biochemistry. He most recently worked for the Sanford Burnham Prebys Medical Research Institute in Lake Nona, Florida, as a professor and program director and ultimately scientific director. He joined Johns Hopkins All Children’s in 2018.

Honors and Awards

• Robert T. Wong Lectureship, John A. Burns School of Medicine at the University of Hawaii, 2019
• J. Lipid Res. Distinguished Lectureship, 2015 Keystone Conference on Crossroads of Lipid Metabolism and Diabetes, 2015 
• Key Note Bollum Biochemistry Symposium U. Minnesota, 1998
• UCI Chancellor’s Award for Mentoring Undergraduate Research, 1998
• Wu Lectureship Columbia U. Institute of Human Nutrition, 1997
• Distinguished Visiting Scholar, Shirahama Conference Japan, 1994
• Established Investigator AHA, 1993 to 1998
• UCLA Microbiology Department Sydney Rittenberg Graduate Student Award, 1983
• UCLA Alumni Foundation Outstanding Graduate Student Award, 1983
• NIH Genetics and Regulatory Mechanisms raining Fellowship, 1979 to 1982
• UC Regents Intern Fellowship (UCLA), 1978 and 1983

Research Interests

Dr. Osborne’s interest in the regulation of cholesterol and fatty acid metabolism and their interconnectedness has been expanded to determine how lipid metabolism is integrated into more global aspects of physiology and cell biology. A major focus of his work has been on the sterol regulatory element binding proteins (SREBPs) and over the past 20 years his lab has made and validated several molecular reagents and assay systems for studying SREBPs using in vitro, cell culture and whole animal model systems.

His team was among the first to demonstrate that nutrient (cholesterol) regulation is associated with chromatin modification changes in promoters for genes regulated by cholesterol. His more recent studies combine animal knockout and genome-wide approaches that indicate SREBPs are at the intersection of nutrient sensing and many other cell-environment interactions including responses to organic and biological threats. This is particularly important in immune cells, which participate as a first line of defense against external threats and his lab has uncovered a role for SREBPs in regulating immune cell metabolism during an inflammatory response.

The mammalian liver is an incredible organ that is a master regulator of whole body metabolism. Because the liver is key to regulating whole body lipid metabolism, the hepatic action of SREBPs has been a major focus for Dr. Osborne’s lab. His team also is interested in additional mechanisms that influence hepatic lipid metabolism and has identified a novel lysine methyl transferase—SETDB2—that is increased during fasting in the liver, a time when SREBPs are shut off. They have identified a role for SETDB2 in shutting off SREBP activity during fasting and have embarked on a more thorough understanding of the role for SETDB2 in regulating liver metabolism during fasting.

In a newer area of research, Dr. Osborne has established a collaboration with Dr. Steven Smith from AdventHealth to explore epigenetic regulation of human adipocyte gene expression. When women gain weight, they deposit excess subcutaneous adipose tissue in one of two patterns: around the abdominal mid-section (“apple” shape) or in the gluteal/femoral region or hips and thighs (“pear” shape). As men gain weight, they tend to gain more weight around their midsection, similar to apple-shaped women. This pattern of weight deposition has been in the clinical literature for decades and more recent studies have shown that “pears” are protected from developing the obesity-related metabolic disease whereas “apples” are more susceptible. The molecular basis for this distinction and what role the different subcutaneous adipose tissues have in regulating metabolic disease progression is unknown.

In previous studies, Dr. Smith and colleagues have compared gene expression patterns in biopsy samples from abdominal vs. gluteal/femoral adipocytes from “pear” shaped women and the studies revealed there are differentially expressed genes. Importantly, a significant fraction of the differential gene expression pattern was maintained when gene expression was compared from cultured pre-adipocytes isolated from the two different depots. Because the differential gene expression pattern was partially maintained when cells were cultured in vitro, it suggested that differential epigenetic patterning might be involved.

In preliminary studies from Dr. Osborne and Dr. Smith’s currently funded project they showed that several differentially expressed genes contain differential histone modification patterns consistent with their gene expression profile. The goal of the funded grant is to investigate this on a genome wide scale in both women and men with the long term goal of trying to determine if the differential gene expression patterns might help provide a mechanism for why “apples” (and men) are more susceptible to the development of metabolic disease relative to “pears.”

Dr. Osborne's research interests include:

• Metabolic regulation of gene expression
• Regulatory interactions between lipid metabolism and cell growth
• Metabolic origins of disease

Select Publications

• Roqueta-Rivera M, Esquejo RM, Phelan PE, Sandor K, Daniel B, Foufelle F, Ding J, Li X, Khorasanizadeh S, Osborne TF. SETDB2 link glucocortoid to lipid metabolism through Insig2a regulation. Cell Metab. 2016 Sept 13; 24(3):474-484. PMCID: PMC5023502
• Kim KY, Jang HJ, Yang YR, Park KI, Seo J, Shin IW, Jeon TI, Ahn SC, Suh PG, Osborne TF, Seo YK. SREBP-2/PNPLA8 axis improves non-alcoholic fatty liver disease through activation of autophagy. Sci Rep. 2016 Oct 21;6:35732. doi: 10.1038/srep35732. Erratum in: Sci Rep. 2016 Nov 29; 6:37794. PMID:27767079
• Lee JH, Phelan P, Shin M, Oh BC, Han X, Im SS, Osborne TF. SREBP-1a-stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1. Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12228-E12234. doi: 10.1073/pnas.1813458115. Epub 2018 Dec 10. PMID:30530672
• Divoux A, Sandor K, Bojcsuk D, Talukder A, Li X, Balint BL, Osborne TF, Smith SR. Differential open chromatin profile and transcriptomic signature define depot-specific human subcutaneous preadipocytes: primary outcomes. Clin Epigenetics. 2018 Nov 26;10(1):148. doi: 10.1186/s13148-018-0582-0. PMID: 30477572

Publication Links

National Center for Biotechnology Information