The Mount Sinai Bone Program

Members of The Mount Sinai Bone Program have made seminal discoveries on the mechanisms of musculoskeletal homeostasis in health and disease. These have included the first description of calcium sensing in the osteoclast, the cell that resorbs bone, as a primary physiologic mechanism for its control by ambient calcium. They discovered that nitric oxide regulates bone remodeling, an observation that has led to the testing of nitric oxide donors for use in human osteoporosis. More recently, his group has established the existence of a novel pituitary-bone axis, which has revolutionized the way how endocrine physiology is viewed. In this new arm of skeletal regulation, the pituitary hormones TSH, ACTH, FSH and oxytocin, previously thought solely to stimulate target endocrine organs, bypass these organs to directly affect the skeleton.

These studies thus implicate pituitary hormones in the pathophysiology of osteoporosis, shifting the paradigm from our traditional, one disease-one hormone hypothesis to a multifaceted pathophysiology with significant future therapeutic implications. In addition, the group focuses on the effects of genetic diseases, including Gaucher Disease and congenital adrenal hyperplasia on the skeleton, the role of the nervous system and muscle in skeletal regulation using spinal cord injury models, mechanisms that regulate cartilage homoeostasis, the crossover of anti-cancer and anti-osteoporosis drugs, and the use of stem cells to promote skeletal regeneration. 

 

Date

Project/Grant

2010 

National Institutes of Health

 

ARRA Supplement to R01 AG 23176-08 

 

2010 - 2011

National Institutes of Health ARRA

 

Supplement to R01 DK 080459-03

 

2008 – 2013

National Institutes of Health R01 (AG 23176-08)

 

Role of FSH in skeletal remodeling

 

2008 – 2013

National Institutes of Health, R01 (DK 080459-03)

 

TSH and bone

 

2004 – 2015

National Institutes of Health R01 (DK 70526-12)

 

Role of oxytocin in bone remodeling            

 

Total costs: $2,658,955 [Pending]                                

MacIntyre, I., Zaidi, M., Alam, A.S.M.T., Datta, H.K., Moonga, B.S., Lidbury, P.K., Hecker, M.R., Vane, J.R. (1991) Osteoclast inhibition: an action of nitric oxide not mediated by cyclic GMP. Proceedings of the National Academy of Sciences 88, 2936-2940.

Zaidi, M., Shankar, V.S., Tunwell, R.E., Adebanjo, O.A., Pazianas, M., Simon, B., Rifkin, B.R., Venkitaraman, A., Huang, C.L.-H., Lai, F.A. (1995) A ryanodine receptor-like molecule in the osteoclast plasma membrane is a functional component of the osteoclast Ca2+ sensor. Journal of Clinical Investigation 96, 1582-1590.

Adebanjo, O.A., Moonga, B.S., Yamate, T., Sun, L., Abe, E., Zaidi, M. (1998) Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracellular Ca2+ sensing in the regulation of osteoclastic bone resorption. Journal of Cell Biology 142, 1349-1356.

Biswas, G, Adebanjo, O.A., Freedman, B.D., Anandatheerthavarada, H.K., Vijayasarthy, C., Zaidi, M., Kotlikoff, M., Avadhani, N.G. (1999) Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle cross-talk. EMBO Journal 18, 522-533.

Adebanjo, O.A., Anandathreethavarada, H.K., Koval, A.P., Moonga, B.S., Biswas, G., Sun, L., Sodam, B.R., Bevis, P.J.R., Huang, C.L.-H., Epstein, S., Lai, F.A., Avadhani, N.G., Zaidi, M. (1999) A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis. Nature Cell Biology 7, 409–414.

Sun, L., Adebanjo, O.A., Moonga, B.S., Corsideo, S., Anandathreethavarada, H.K., Biswas, G., Toshiya, A., Hakeda, Y., Koval, A., Sodam, B.R., Bevis, P.J.R., Moser, A.J., Lai, F.A., Epstein, S., Troen, B.R., Kumegawa, M., Zaidi, M. (1999) CD38/ADP-ribosyl cyclase: a new role in the regulation of osteoclastic bone resorption. Journal of Cell Biology 146, 1161-1171.

Sun, L., Adebanjo, O.A., Koval, A., Anandathreethavarada, H.K., Iqbal, I., Wu, X.Y., Moonga, B.S., Wu, X.B., Biswas, G., Bevis, P.J.R., Kumegawa, M., Epstein, S., Huang, C.L.-H., Avadhani, N.G., Abe, E., Zaidi, M. (2002) A novel mechanism for coupling cellular intermediary metabolism to cytosolic Ca2+ signaling via CD38/ADP-ribosyl cyclase, a putative intracellular NAD+ sensor. FASEB Journal 16, 302-314.

Sun, L., Iqbal, J., Dolgilevich, S., Yuen, T., Wu, X.-B., Moonga, B.S., Adebanjo, O.A., Bevis, P.J.R., Lund, F., Huang, C.L.-H., Blair, H.C., Abe, E., Zaidi, M. (2003) Disordered osteoclast formation and function in CD38 (ADP-ribosyl cyclase)-deficient mouse establishes an essential role for CD38 in bone resorption. FASEB Journal 17, 369-375.

Wu, X.-B., Li, Y., Schneider, A., Yu, W., Gopalan, R., Yamamoto, M., Alam, M., Brunet, L.J., Harland, R.M., Blair, H.C., Zaidi, M., Abe, E. (2003) Impaired osteoblastic differentiation, reduced bone formation and severe osteoporosis in noggin-overexpressing. Journal of Clinical Investigation 112, 924-934.

[1]Abe, E., Marians, R., Wu, X-B., Iqbal, J., Ando, T., Blair, H.C., Davies, T.F., Zaidi, M. (2003) TSH is a negative regulator of bone remodelling. Cell 175, 151-162.

Zaidi, M. (2005) Preview Article: Neural surveillance of skeletal homeostasis. Cell Metabolism 1, 219-221.

Sun, L., Blair, H.C., Peng, Y., Zaidi, N., Adebanjo, O.A, Wu, X.B., Wu, X.Y., Iqbal, J., Epstein, S., Abe, E., Moonga, B.S., Zaidi, M. (2005) Calcineurin regulates bone formation by the osteoblast. Proceedings of the National Academy of Sciences 47, 17130-17135.

[2]Sun, L., Zhang, Z., Iqbal, J., Zaidi, S., Papachristou, D.J., Zhou, H., Sharrow, A.C., Peng, Y., Yaroslavskiy, B.B., Zhu, L.-L., Zallone, A., Sairam, M.R. Kumar, T.R., Landa, L.C., Schaffler, M.B., Moonga, B.S., Blair, H.C., Zaidi, M. (2006) FSH directly regulates bone mass. Cell 125, 247-260.

Hase, H., Ando, T., Eldeiry, L., Brebene, A., Peng, Y., Lin, L., Amano, H., Davies, T.F., Sun, L., Zaidi, M., Abe, E. (2006) TNF mediates the skeletal effects of TSH. Proceedings of the National Academy of Sciences 103: 12849-12854.

Iqbal, J., Sun, L., Kumar, T.R., Blair, H.C., Zaidi, M. (2006) FSH stimulates TNF production from immune cells to trigger osteoclast and osteoblast formation. Proceedings of the National Academy of Sciences. 103: 14925-14930.

Zaidi, M. (2007) Skeletal remodeling in health and disease. Nature Medicine 13: 791-801.

Sun. L., Vukicevic, S., Baliram, R., Yang, G., Sendak, R., McPherson, J., Zhu, L.L., Iqbal, J., Latif, R., Natrajan, A., Arabi, A., Yamoah, K.O.S.J., Moonga, B.S., Gabet, Y., Davies, T.F., Bab, I., Abe, E., Sampath, K., Zaidi, M. (2008) Intermittent recombinant TSH injection prevents ovariectomy-induced bone loss. Proceedings of the National Academy of Sciences 105: 4289-4294.

Tamma, R., Colaianni, G., Zhu, L.L., DiBenedetto, A., Greco, G., Montemurro, G., Patano, N., Strippoli, M., Vergari, R., Mancini, L., Colucci, S., Grano, M.m Faccio, R., Liu, X., Li, J., Usmani, S., Nishimori, K., Young, L., Bachar, M., Bab, I., Buettner, C., Iqbal, J., Sun, L., Zaidi, M., Zallone, A. (2008) Oxytocin is an anabolic bone hormone. Proceedings of the National Academy of Sciences 106: 7149-7154.

Iqbal, J., Sun, L., Zaidi, M. (2009) Coupling bone degradation and formation. Nature Medicine 15: 729-731.

Zaidi, M., Sun, L., Robinson, L.J., Tourkova, I.L., Liu, L., Wang, Y., Zhu, L.L., Liu, X., Liu, J.H., Peng, Y.Z., Yang, G., Sun, H., Levine, A., Iqbal, J., Yaroslavskiy, B.B., Isales, C., Blair, H.C. (2010) ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proceedings of the National Academy of Sciences 107: 8782-8787.

[1] Accompanying editorials in Nature, Cell and Science
[2] Accompanying editorials in Nature Medicine and Cell Metabolism

Selected Honors and Awards are listed below:

Mone Zaidi

 

2010  

Laurea Honoris Causa (Honorary Doctorate in Medicine), University of Bari, Italy, 2010

Lectio Magistralis, University of Bari, 2010

2010

Member, College of CSR Reviewers, NIH

2010

Leo Sreebny Distinguished Lecture, State University of New York, Stony Brook

2009

Annual E.R. Marookian Lecture, University of Pennsylvania School of Veterinary Medicine

2009

Rudin-Kase Dean’s Molecules to Man Lectures, Icahn School of Medicine

2008

Professor S.H. Zaidi Memorial Oration, Indian Toxicology Research Institute, India

2007

Kramer Visiting Professor, Dartmouth Medical School

2006

Highlight Speaker, National Institute on Aging (NIA) Council

2006

Guest Speaker, Japanese Society for Bone and Mineral Research

2005

Elected as Member, Association of Osteobiology

2004

Elected as Member, Interurban Clinical Club [Councilor for New York, 2010-2013]

2004

Elected as Association of American Physicians

2002-2003

Chair, NIH Orthopedics and Musculoskeletal Study Section

2003-2006

Chair, VA Merit Review Study Section

 

 

Terry Davies

 

2010

Stanbury Award and Lecture, American Thyroid Association 

2009

President, American Thyroid Association

2004-2008 

Editor-in-Chief, Thyroid

2003

Sydney Ingbar Memorial Lecture, American Thyroid Association

2000 

Elected to Association of American Physicians

 

 

Li Sun

 

2005

Award for the Most Outstanding Research, American Society for Bone and Mineral Research

 

 

Jameel Iqbal

 

2006 

Anthony Means Award for Basic Science, Endocrine Society

2007 

Research Achievement Award, Mount Sinai Graduate School of Biological Sciences

 2007 

Dr. Milton Brothers Memorial Award for Excellence in Endocrinology, MSSM

 2008

American Federation for Aging Research Fellowship, 2008

Mone Zaidi, MD, PhD, FRCP
Professor of Medicine
Director, The Mount Sinai Bone Program

Li Sun, MD, PhD
Associate Professor of Medicine
Co-Director, The Mount Sinai Bone Program

Terry Davies, MD, FRCP
Baumritter Professor of Medicine
Principal Investigator and Co-Director, The Mount Sinai Bone Program

Solomon Epstein, MD, FRCP
Professor of Medicine
Associate Director for Clinical Research

Maria New, MD
Professor of Pediatrics and Genetics

William Bauman, MD
Professor of Medicine
James Peters VA Medical Center

Christoper Cardozo, MD
Associate Professor
James Peters VA Medical Center

Weiping Qin, MD
Assistant Professor
James Peters VA Medical Center

Jeffrey Mechanick, MD
Clinical Professor of Medicine

Herb Sun, PhD
Assistant Professor of Orthopedics

Jameel Iqbal, MS, PhD
Associate Scientist and Senior Fellow

 

Jianhua Li

Senior Technician

Alberta Zallone, PhD

Distinguished Visiting Professor

Barry R. Rifkin, DDS, PhD

Visiting Professor

Simon Mendez-Ferrera

Visiting Scientist

To find our clinical trials please go here:  http://icahn.mssm.edu/research/clinical-trials