Chester Brown, M.D., Ph.D.
Assistant Professor, Department of Molecular and Human Genetics
Education
B.S., Howard University, 1985
Ph.D., University of Cincinnati, 1993
M.D., University of Cincinnati College of Medicine, 1993
Board Certifications
American Board of Medical Genetics: Clinical Genetics
American Board of Pediatrics
Professional Organizations
Member, American Society of Human Genetics
Member, The Endocrine Society
Member, National Medical Association
Fellow, American Academy of Pediatrics
Clinical Interests
Birth defects, endocrinopathies and disorders of growth.
Research Interests
Our laboratory is interested in understanding the roles that members of the transforming growth factor beta (TGF-β) superfamily play in regulating body composition, with a particular emphasis on the mechanisms that regulate adiposity. Our approach is to modify specific genes in mice to determine their normal functions. These genes can be either completely inactivated or can be replaced by closely related genes. By studying the physiologic effects of these mutations on the mice as a whole as well as the characteristics of cells that are derived from them, we are able to better understand the complex interrelationships of TGF-β signaling, incorporating state of the art technologies to assess effects of the mutations at the physiologic, biochemical, and molecular levels.
Testis from a normal mouse (left) compared to those from knock-in mice with one (right) or two (center) copies of a hypomorphic knock-in allele at the activin beta A locus.
Activins are TGF-β family members that are important for many biological processes, including normal growth and development of the fetus. Mice that are completely missing one activin family member, activin βA, die shortly after birth due to a variety of birth defects. Our previous studies have demonstrated that a closely related substitute gene can be used to correct activin βA deficiency if the substitute is turned on at the correct time and in the correct location. This is an important observation, because it gives us one way to study the functions of genes that when completely inactive result in early death (such as activin βA). We have used this gene substitution strategy to replace activin βA with its closely related family member, activin βB. These mice survive but grow more slowly than normal and have almost no body fat, revealing previously unrecognized roles for activins in regulating body size and composition through their influence on mitochondrial energy metabolism. The severity of these features is influenced substantially by the dose of the substitute gene. Drug-inducible Cre-recombinase technology combined with microarray analysis is also used in our laboratory to study gene function, allowing us to reversibly control the expression of any gene of interest in specific tissues or in all tissues at specific points in time and then to examine the effects of these changes on genome-wide gene expression.
Our studies have given us considerable insight into the normal roles of activin signaling and that of other TGF-β superfamily members. Moreover, the high tolerance for substitute genes observed in our studies and others may have important implications with respect to strategies for the treatment of certain genetic disorders. Our ultimate goal is to understand how TGF-β superfamily signaling may play similar roles in humans and has provided the basis for the rational design of potential drugs for the treatment of cachexia, obesity, and diabetes.
Selected Publications
- Li L, Shen JJ, Bournat JC, Huang L, Chattopadhyay A, Li Z, Shaw C, Graham BH, Brown CW (2009). Activin signaling: effects on body composition and mitochondrial energy metabolism. Endocrinology 150(8): 3521-9. [Pub Med]
- Jiang Y, Fang P, Adesina AM, Furman P, Johnston JJ, Biesecker LG, Brown CW (2009). Molecular characterization of co-existing Duchenne muscular dystrophy and oculo-facio-cardio-dental syndrome in a girl. Am. J. Med. Genet. A. 149A(6): 1249-52. [Pub Med]
- Shen JJ, Huang L, Li L, Jorgez C, Matzuk MM, Brown CW (2009). Deficiency of growth differentiation factor 3 protects against diet-induced obesity by selectively acting on white adipose. Mol. Endocrinol. 23(1): 113-23. [Pub Med]
- Pangas SA, Jorgez CJ, Tran M, Agno J, Li X, Brown CW, Kumar TR, Matzuk MM (2007). Intraovarian activins are required for female fertility. Mol. Endocrinol. 21(10): 2458-71. [Pub Med]
- Chen C, Ware SM, Houston-Hawkins DE, Matzuk MM, Shen MM, Brown CW (2006). The Vg1-related protein GDF3 regulates Nodal expression in the pre-gastrulation mouse embryo. Development 133(2): 319-29. [Pub Med]
- Brown CW, Li L, Houston-Hawkins DE, Matzuk MM (2003). Activins are critical modulators of growth and survival. Mol. Endocrinol. (12): 2404-17. [Pub Med]
- Chang H, Brown CW, Matzuk MM (2002). Genetic analysis of the mammalian TGF-β superfamily. Endocr. Rev. 23(6): 787-823. [Pub Med]
- Brown CW, Houston-Hawkins DE, Woodruff TK, Matzuk MM (2000). Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Nat. Genet. 25(4): 453-7. [Pub Med]
Contact Information
Chester Brown, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.
Room: ABBR-R717
Phone: 713-798-7418
Fax: 713-798-8920
E-mail: