Mark Roberson, PhD
Department of Biomedical Sciences
Professor Emeritus of Physiology
Department of Biomedical Sciences
Cornell University College of Veterinary Medicine
T5 010B Veterinary Research Tower, Box 18
Ithaca, NY 14853-6401
The Roberson Laboratory is focused on the molecular endocrinology of the reproductive axis with specific emphasis on cell signaling and transcriptional mechanisms within the gonadotrope of the anterior pituitary gland and the trophoblast cell lineages of the primate and mouse placentas. The initial focus and development of our research enterprise was/is centered around biosynthesis and secretion of the gonadotropic hormones human chorionic gonadotropin (hCG), luteinizing hormone (LH) and follicle stimulating hormone (FSH). This includes studies examining the role and requirement of Ca+2/ERK/MAPK signaling within the pituitary gonadotrope within the gonadotropin releasing hormone (GnRH) signaling network; and placental-specific transcription factors (such as distal-less 3 or Dlx3) on production of hCG, placental vascular morphogenesis at the maternal/fetal interface and studies related to the development and differentiation of placental trophoblasts.
The Roberson Lab has been instrumental in the development of key in vivo mouse models examining the role and requirement for extracellular signal-regulated protein kinase (ERK) 1 and 2 signaling pathways within the neuroendocrine axis on fertility in male and female mice as a model system. ERKs are kinases that control intracellular behavior by reversible phosphorylation of target proteins; for example, GnRH can induce ERK activation which leads to the activation of transcriptional regulators like early growth response factor 1 (Egr1) controlling LH synthesis. Our published studies helped to define the importance and molecular mechanisms associated with extracellular calcium influx within the gonadotrope on productive GnRH/ERK signaling; the role of GnRH-inducible, ERK-dependent dual specificity phosphatases which form an intracellular negative feedback loop within the gonadotrope governing the magnitude and duration of ERK signaling, particularly during prolonged GnRH exposure like during the preovulatory surge of GnRH/LH; the biophysical organization of the GnRH receptor within discrete cholesterol-enriched domains within the plasma membrane termed membrane rafts and the requirement for raft localization of this receptor to facilitate GnRH/ERK signaling; the development of in vivo mouse models of conditional ERK deletion within the GnRH and kisspeptin neurons of the hypothalamus, the pituitary gonadotrope, the oocyte and the testes and the role this pathway plays to maintain and support fertility; the role of the actin cytoskeleton in the regulation of gonadotrope cellular behavior and secretion of LH; and most recently, the use of deep sequencing and proteomic analyses on the peptides associated with the GnRH receptor within the raft and the measured transcriptional outcome of a GnRH pulse in the presence or absence of a functional ERK signaling pathway. Collectively, these studies have moved our field of neuroendocrine regulation of reproduction and fertility forward dramatically.
The current research in the Roberson lab seizes on these comprehensive data sets and identifies the unique presence of a bile acid receptor within the hypothalamus and pituitary gonadotrope and how bile acids may serve as an indicator of energy status in the gonadotrope and the whole animal. Bile acids have been known for decades to regulate lipid digestion in the gut. Recently, receptors for bile acid have been identified and bile acids themselves are now clearly recognized to have endocrine signaling function in many physiological systems including the liver, gut, brain and the reproductive system. Our studies have shown that bile acid regulation of a GPCR termed TGR5 modulates the timing of the pubertal transition in adolescent female mice. Further, metabolomic studies demonstrate liver production of bile acids changes remarkable early in the pubertal transition both in terms of level of primary bile acid production and changes in the conjugation status of specific bile acid isoforms just prior to expression of TGR5 in the mediobasal hypothalamus. We are actively working to dissect the mechanisms associated with the role of TGR5 on changes in the reproductive axis during puberty.
- Postdoctoral Fellow, Oregon Health Sciences University and the University of Iowa (1990-1995)
- PhD, University of Nebraska, 1990
- MS, Montana State University, 1984
- BS, California Polytechnic State University, 1981
Dr. Roberson was raised in northern California and his early academic training focused on animal science, physiology and agriculture. Following the completion of his PhD program, Dr. Roberson shifted focus and began training in molecular endocrinology. As a postdoctoral fellow at the medical schools at the University of Iowa and Oregon Health and Sciences University, he completed a number of studies examining specific transcriptional mechanisms and cell signaling events which controlled the production and secretion of pituitary gonadotropins. Dr. Roberson leveraged this training and began a faculty appointment in the (then) Department of Physiology in the College of Veterinary Medicine at Cornell University in 1995. He was promoted to Associate Professor with indefinite tenure in 2001 in the Department of Biomedical Sciences (which included the former Department of Physiology). In 2007, Dr. Roberson was appointed Chair of Biomedical Sciences; a position he held until 2017 when he returned to the faculty ranks. In 2008, Dr. Roberson was promoter to Professor.
Reproductive state and choline intake influence enrichment of plasma lysophosphatidylcholine-DHA: a post hoc analysis of a controlled feeding trial. Klatt KC, McDougall MQ, Malysheva OV, Brenna JT, Roberson MS, Caudill MA.Br J Nutr. 2019 Dec 14;122(11):1221-1229. doi: 10.1017/S0007114519002009.PMID: 31782377
Maternal choline supplementation alters vitamin B-12 status in human and murine pregnancy. King JH, Kwan STC, Bae S, Klatt KC, Yan J, Malysheva OV, Jiang X, Roberson MS, Caudill MA.J Nutr Biochem. 2019 Oct;72:108210. doi: 10.1016/j.jnutbio.2019.07.001. Epub 2019 Jul 8.PMID: 31473512
Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse. Brown JL, Sones JL, Angulo CN, Abbott K, Miller AD, Boehm U, Roberson MS.Sci Rep. 2019 Jul 3;9(1):9641. doi: 10.1038/s41598-019-45997-0.PMID: 31270345
Maternal Choline Supplementation Modulates Placental Markers of Inflammation, Angiogenesis, and Apoptosis in a Mouse Model of Placental Insufficiency. King JH, Kwan STC, Yan J, Jiang X, Fomin VG, Levine SP, Wei E, Roberson MS, Caudill MA.Nutrients. 2019 Feb 12;11(2):374. doi: 10.3390/nu11020374.PMID: 30759768
Maternal Choline Supplementation during Normal Murine Pregnancy Alters the Placental Epigenome: Results of an Exploratory Study. Kwan STC, King JH, Grenier JK, Yan J, Jiang X, Roberson MS, Caudill MA.Nutrients. 2018 Mar 28;10(4):417. doi: 10.3390/nu10040417.PMID: 29597262
Sex- and Age-Specific Impact of ERK Loss Within the Pituitary Gonadotrope in Mice. Brown JL, Xie J, Brieño-Enriquez MA, Sones JL, Angulo CN, Boehm U, Miller A, Toufaily C, Wang Y, Bernard DJ, Roberson MS.Endocrinology. 2018 Mar 1;159(3):1264-1276. doi: 10.1210/en.2017-00653.PMID: 29300908
Maternal Choline Supplementation Modulates Placental Nutrient Transport and Metabolism in Late Gestation of Mouse Pregnancy. Kwan STC, King JH, Yan J, Wang Z, Jiang X, Hutzler JS, Klein HR, Brenna JT, Roberson MS, Caudill MA.J Nutr. 2017 Nov;147(11):2083-2092. doi: 10.3945/jn.117.256107. Epub 2017 Sep 20.PMID: 28931587
Maternal Choline Supplementation Alters Fetal Growth Patterns in a Mouse Model of Placental Insufficiency. King JH, Kwan STC, Yan J, Klatt KC, Jiang X, Roberson MS, Caudill MA.Nutrients. 2017 Jul 18;9(7):765. doi: 10.3390/nu9070765.PMID: 28718809
DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells. Li S, Roberson MS.Sci Rep. 2017 May 17;7(1):2009. doi: 10.1038/s41598-017-02120-5.PMID: 28515447
Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner. Kwan STC, King JH, Yan J, Jiang X, Wei E, Fomin VG, Roberson MS, Caudill MA.Placenta. 2017 May;53:57-65. doi: 10.1016/j.placenta.2017.03.019. Epub 2017 Mar 30.PMID: 28487022
Awards and Honors
Dr. Roberson has received near uninterrupted research funding from federal agencies such as the NIH and USDA. He was Director of the Reproductive Sciences and Genomics Training Program for 10 years, an NICHD-funded program supporting the training and professional development of graduate students and postdoctoral trainees. Along with several colleagues, Dr. Roberson was a founding member of the Center for Reproductive Genomics at Cornell University. He has served on numerous editorial boards in the field of endocrinology; made significant contributions to the Endocrine Society, particularly in the area of career development and minority affairs; is a long standing instructor in the Frontiers in Reproduction course at the Marine Biology lab at Woods Hole, MA; and has made important contributions to grant review groups at the federal (NIH and USDA) and state (PA Department of Health) levels. Dr. Roberson currently serves as Director of Undergraduate Studies in Animal Physiology within the biology major and directs the Honors Program in Animal Physiology at Cornell. He teaches physiology/pathophysiology in the preclinical veterinary curriculum and Principles of Animal Physiology to undergraduate biology majors.