emblem राष्ट्रीय प्रतिरक्षाविज्ञान संस्थानNational Institute of ImmunologyAn Autonomous Institute of Dept. of Biotechnology, Ministry of Science and Technology, Govt. of India

Dr. Vijay K. Yadav

Research Interest:

The focus of the laboratory is to use mouse genetic, genomic, and proteomic approaches to investigate how molecules originating from within, and outside the skeleton regulate its physiology, and how skeleton in turn regulates whole-body energy homeostasis.

Summary of Research:

The lab aims to identify novel functional connections between organs and to unravel factors that underlie human metabolism and its disorders. To do so we use skeleton as an organ system and investigate its connections with other organs and the mouse as a model organism. The skeleton in our body is like a house. A house is constantly deteriorating due to external factors, such as sunlight and rain, internal factors such as rusting or woodworm. In the same way our skeleton can deteriorate due to factors that originate within and outside the skeleton. For example, alterations in the levels and/or action of certain cytokines or hormones can lead to changes in bone density. The best example of this phenomenon is the loss of estrogen- an ovary-derived hormone- after menopause, which can result in increased bone loss and can lead ultimately to osteoporosis. This fact underscores that systemic influences or molecules originating in other organs are central to the regulation of bone mass. Skeleton in turn signals through the secretion of hormones viz., osteocalcin to regulate the function of these organs and contributes in the regulation of whole-organism physiology.

Over the last few years we have identified a novel gut-liver-bone endocrine axis operational through vitamin B12 (B12) and delineated the road map of B12  action on bone. Using a mouse genetic model of loss of function of gastric intrinsic factor (Gif), the protein that is essential for the absorption of B12, we have identified the pathway linking B12 action in the liver to new bone formation. In the liver B12 regulates in a GH-dependent manner production of taurine that is then released  into  the  circulation  and  acts  on  the  bone  cells  to  impact,  specifically, new  bone formation. The discovery of this unanticipated pathway between gut, liver and bone would not have been possible without the use of mouse molecular genetics and studies in the clinic that allowed us to understand interactions between these organs. Moreover, the fact that the B12- taurine-bone pathway affects only bone formation and appears to play the same role in mice and human beings raises the prospect that targeting this pathway through pharmacological means could be a novel approach toward an anabolic treatment of osteoporosis. Current studies in this founding project aim at unraveling the signaling pathways in the liver and in bone that regulate this endocrine axis. We continue to identify and investigate functions of other novel endocrine molecules that regulate bone mass and to harness their potential in treating skeletal diseases.

Thus the overall goal is to elucidate novel endocrine interactions between bone and other organs using mouse and human genetic models to identify novel and adapted therapies to cure bone and other metabolic disorders.

Awards:
• Ramalingaswamy Fellowship Award, Department of Biotechnology, Government of India: 2016.
• National Institute of Health (USA) Pathway to Independence Award (K99/R00): 2009.
• Elected to Columbia University Senate, NY, USA: 2009-2010.
• International Bone and Mineral Society Young Investigator Committee, 2009-2013.
• John Haddad Young Investigator Award, American Institute of Mineral Metabolism, 2009.
• Gideon and Sevgi Rodan Fellowship Award, 2008-2009.
• Young Investigator Award, American Society of Bone and Mineral Research, 2007.
• Professor G.P. Talwar Award by the Society for the study of reproduction and fertility, India 2003.
• Junior/Senior Research Fellowship, Council of Scientific and Industrial Research (CSIR), India 2001-2005.
• University topper (M.Sc.), Dept of Biochemistry, University of Lucknow, 1999.
• College topper, Pre-graduation level (XII), RDS Inter College, India, 1994.

Patents:
WO/2010/056992: Methods of diagnosing, preventing and treating low bone mass diseases.
P4078PC00/IR2579: Methods of suppressing appetite by the administration of antagonists of the serotonin Htr1a or Htr2b receptors or inhibitors of Tph2.

Publications:
  • Sharan Kunal, Lewis Kirsty, Furukawa Takahisa, Yadav Vijay K.# (2017) Regulation of bone mass through pineal-derived melatonin-MT2 receptor pathway. J Pineal Research. 2017 Sep;63(2). doi: 10.1111/jpi.12423
  • Lewis Kirsty*, Sharan Kunal *, Takumi Toru, Yadav Vijay K.#. (2017) Skeletal Site-specific Changes in Bone Mass in a Genetic Mouse Model for Human 15q11-13 Duplication Seen in Autism. Scientific Reports. 2017 Aug 29;7(1):9902
  • Oh CM, Namkung J, Go Y, Shong KE, Kim K, Kim H, Park BY, Lee HW, Jeon YH, Song J, Shong M, Yadav VK, Karsenty G, Kajimura S, Lee IK, Park S, Kim H. (2015) Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nature Communications. 2015 Apr 13;6:6794. doi: 10.1038/ncomms7794.
  • Kim K, Oh CM, Ohara-Imaizumi M, Park S, Namkung J, Yadav VK, Tamarina NA, Roe MW, Philipson LH, Karsenty G, Nagamatsu S, German MS, Kim H. (2015) Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state. Endocrinology. 2015 Feb; 156(2):444-52.
  • Roman-Garcia P*, Quiros-Gonzalez I*, Mottram L*, Lieben L, Sharan K, Wangwiwatsin A, Tubio J, Lewis K, Wilkinson D, Santhanam B, Sarper N, Clare S, Vassiliou GS, Velagapudi VR, Dougan G, Yadav VK# (2014) Vitamin B12-dependent taurine synthesis regulates growth and bone mass. J Clin Invest. 2014 Jul 1;124(7):2988-3002. * equal contribution
  • Quiros-Gonzalez I, Yadav VK# (2014) Central genes, pathways and modules that regulate bone mass. Arch Biochem Biophys. 2014 Nov 1;561:130-6
  • Sharan K, Yadav VK# (2014) Hypothalamic regulation of bone mass. Best Practice & Research Clinical Endocrinology & Metabolism. 2014 Oct;28(5):713-23
  • Yadav VK# (2013) Serotonin: The Central Link between Bone Mass and Energy Metabolism in Translational Endocrinology of Bone. Elsevier Press. 815-23.
  • arcOGEN Consortium; arcOGEN Collaborators, Zeggini E, Panoutsopoulou K, Southam L, Rayner NW, Day-Williams AG, Lopes MC, Boraska V, Esko T, Evangelou E, Hoffman A, Houwing-Duistermaat JJ, Ingvarsson T, Jonsdottir I, Jonnson H, Kerkhof HJ, Kloppenburg M, Bos SD, Mangino M, Metrustry S, Slagboom PE, Thorleifsson G, Raine EV, Ratnayake M, Ricketts M, Beazley C, Blackburn H, Bumpstead S, Elliott KS, Hunt SE, Potter SC, Shin SY, Yadav VK, Zhai G, Sherburn K, Dixon K, Arden E, Aslam N, Battley PK, Carluke I, Doherty S, Gordon A, Joseph J, Keen R, Koller NC, Mitchell S, O'Neill F, Paling E, Reed MR, Rivadeneira F, Swift D, Walker K, Watkins B, Wheeler M, Birrell F, Ioannidis JP, Meulenbelt I, Metspalu A, Rai A, Salter D, Stefansson K, Stykarsdottir U, Uitterlinden AG, van Meurs JB, Chapman K, Deloukas P, Ollier WE, Wallis GA, Arden N, Carr A, Doherty M, McCaskie A, Willkinson JM, Ralston SH, Valdes AM, Spector TD, Loughlin J. (2012) Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study. Lancet. 380(9844):815-23
  • Yadav VK*, Oury F*, Tanaka KF, Thomas T, Wang Y, Cremers S, Hen R, Krust A, Chambon P, Karsenty G (2011) Leptin-dependent serotonin control of appetite: temporal specificity, transcriptional regulation, and therapeutic implications. J Exp Med. 2011 Jan 17;208(1):41-52.* equal contribution
  • Oury F, Yadav VK, Wang Y, Zhou B, Liu XS, Guo XE, Tecott LH, Schutz G, Means AR, Karsenty G. (2010) CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons. Genes Dev. 2010 Oct 15;24(20):2330-42.
  • Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P (2010) Pharmacological inhibition of gut- derived serotonin is a potential bone anabolic treatment for osteoporosis. Nature Medicine Mar;16(3):308-12
  • Shi Y, Oury F, Yadav VK, Wess J, Liu XS, Guo XE, Murshed M, Karsenty G (2010) Signaling through the muscarinic receptor 3 favors bone mass accrual by decreasing the sympathetic activity. Cell Metabolism, Mar 3;11(3):231-8
  • Yadav VK*, Oury F*, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G (2009) A serotonin- dependent mechanism explains leptin regulation of bone mass, appetite and energy expenditure. Cell. Sep 4;138(5):976-89. * equal contribution
  • Hinoi E, Gao N, Young Jung D, Yadav VK, Yoshizawa T, Myers Jr. MG, Chua Jr. SC, Kim JK, Kaestner KH and Karsenty G. (2008) The sympathetic tone mediates leptin’s inhibition of insulin secretion by modulating osteocalcin bioactivity. J Cell Biol. Dec 29;183(7):1235-42.
  • Shi Y*, Yadav VK*, Suda N, Liu XS, Guo XE, Myers MG Jr, Karsenty G (2008) Dissociation of the Neuronal Regulation of Bone Mass and Energy Metabolism by Leptin in vivo. Proc Natl Acad Sci U S A. Dec 23;105(51):20529-33 * equal contribution
  • Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G (2008) Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. Nov 28;135(5):825-37.
  • Yadav VK and R. Medhamurthy (2006) Dynamic Changes in mitogen activated protein kinases during development, induced-luteolysis and simulated early pregnancy in the bonnet monkey (Macaca radiata): A role of p38 in the regulation of luteal function. Endocrinology 147(4): 2018-27
  • Yadav VK, Lakshmi G, Medhamurthy R (2005) Prostaglandin F2a-mediated activation of apoptotic signaling cascades in the corpus luteum during apoptosis: Involvement of caspase activated DNase J Biol Chem 280(11):10357-67
  • Yadav VK, Muraly P and Medhamurthy R (2004) Identification of Novel Genes Regulated by the Luteinizing Hormone in the Primate Corpus Luteum: Insights into LH-Responsiveness during the Late Luteal Phase. Mol. Human Reprod. ; 10(9):629-639
  • Yadav VK, Sudhagar RR, Medhamurthy R (2002) Apoptosis During Spontaneous and Prostaglandin F2a-Induced Luteal Regression in Buffalo Cow (Bubalus bubalis): Involvement of Mitogen-Activated Protein Kinases. Biology of Reproduction; 67(3): 752-759

# as corresponding author