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Molecular and Cellular Biology

Houston, Texas

Image 1: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.; Image 2: By Yi LI, Ph.D.; Image 3: Mouse oocyte at meiosis I immunostained for tubulin (red) phosphop38MAPK (green) and DNA (blue). By JoAnne Richards, Ph.D.; Image 4: Expanded cumulus cell ooctye ocmplex immunostained for hyaluronan (red), TSG6 (green) and DAN (blue). By JoAnne Richards, Ph.D.; Image 5: Epithelial cells taken from a mouse mammary gland were cultured in a dish and transduced with a retrovirus expressing two genes. The green staining shows green fluorescent protein and the red staining shows progesterone receptor expression. The nucleus of each cell is stained blue. Photomicrograph taken at 200X magnification. By Sandra L. Grimm, Ph.D.; Image 6: Ovarian vasculature (red) is excluded from the granulosa cells (blue) within growing follicles (round structures); Image 7: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.
Department of Molecular and Cellular Biology
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Adam Antebi, Ph.D.

Associate Professor
Huffington Center on Aging, Department of Molecular and Cellular Biology

Education

Ph.D.: Massachusetts Institute of Technology, Cambridge
Postdoctoral training: Johns Hopkins University, Baltimore

Research Interest

Hormonal control of C. elegans metabolism, life stages and aging
All animals develop through successive life stages and have life spans that are determined by their genome and modulated by the environment. By studying the simple roundworm C. elegans we seek to uncover phyletically conserved pathways that determine a species life plan and life span.

My laboratory has focused on a nuclear hormone receptor (NHR) signaling pathway that couples environmental cues, such as nutrient availability, to development, growth and aging. C. elegans DAF-12 is an NHR transcription factor receptor most related to vertebrate vitamin-D and liver-X receptors, and regulates metabolism, dauer diapause, developmental timing, and life span. Our studies reveal that DAF-12 works as part of a hormone regulated switch: The liganded receptor partly promotes reproductive growth and rapid aging, while the unliganded receptor specifies a long-lived developmentally arrested larval stage called the dauer diapause, as well as longevity in adults. Recently, we have identified endogenous DAF-12 ligands to be bile acid-like steroids, providing critical evidence that such molecules regulate animal longevity. We are now exploring the molecular mechanisms by which ligand, receptor complexes, and target genes determine organismal physiology.

DAF-12 also works in the heterochronic circuit, a regulatory hierarchy controlling developmental timing. C. elegans develops through four larval stages (L1-L4) to adult. Mutants in the heterochronic loci cause animals to repeat or delete stage specific cellular programs. Most identified components are conserved, including the first discovered microRNAs. DAF-12 specifies third and later larval stage programs, including gonadal pathfinding and epidermal stem cell division patterns. Through further genetic screens we have identified other heterochronic loci, including a conserved F-box protein called DRE-1. How these various components cooperate to regulate developmental timing is an area of critical interest. Importantly, our finding that DAF-12 links dauer and heterochronic pathways, suggests that this receptor coordinates reproductive maturation to the sustainable environment. Conceivably, estrogen receptor may analogously regulate the pace of maturation in response to dietary, hormonal, and genetic inputs.

Contact Information

Baylor College of Medicine
One Baylor Plaza, Room M320, N803.02
Houston, TX 77030

Phone: 713-798-6661 office; 713-798-2117 lab
Fax: 713-798-4161
E-mail: aantebi@bcm.edu

Selected Publications

  1. Antebi A. (2007). Genetics of aging in C. elegans. Plos Genetics 3:1565-1571.
  2. Fielenbach N, Guardavaccaro D, Neubert K, Chan T, Li D, Feng Q, Hutter H, Pagano M and Antebi A. (2007). DRE-1, an evolutionarily conserved F-box protein that regulates C. elegans developmental age. Dev Cell 12:443-455.
  3. Gerisch B, Rottiers V, Li D, Motola D, Cummins CL, Lehrach H, Mangelsdorf D and Antebi A. (2007). A bile acid-like steroid modulates C. elegans life span and stress resistance through nuclear receptor signaling. PNAS 104:5014-5019.
  4. Rottiers V, Motola D, Cummins CL, Gerisch B, Nishiwaki K, Mangelsdorf D and Antebi A. (2006). Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase. Dev Cell 10:473-82.
  5. Motola D, Cummins CL, Rottiers V, Sharma K, Sunino K, Xu E, Auchus R, Antebi A and Mangelsdorf D. (2006). Identification of hormonal ligands for DAF-12 that govern dauer formation and reproduction in C. elegans. Cell 124:1209-23.
  6. Shostak Y, Van Gilst MR, Antebi A and Yamamoto KR. (2004). Identification of DAF-12 binding sites, response elements and target genes. Genes & Development 18:2529-44.
  7. Ludewig A, Kober-Eisermann C, Weitzel C, Neubert K, Bethke A, Gerisch G, Hutter H and Antebi A. (2004). A novel coregulator/nuclear receptor complex controls C. elegans larval development, fat metabolism and aging. Genes & Development 18:2120-33.
  8. Gerisch B and Antebi A. (2004) Hormonal signals produced by DAF-9/cytochrome P450 regulate C. elegans dauer diapause in response to environmental cues. Development 131:1765-76.
  9. Tatar M, Bartke A and Antebi A. (2003). Endocrine Regulation of Aging by Insulin-like signals. Science 299:1346-51.
  10. Gerisch B, Weitzel C, Kober-Eisermann C, Rottiers V and Antebi A. (2001). A hormonal signaling pathway influencing C. elegans metabolism, reproductive development and life span. Dev. Cell 1:841-851.

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