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Research in Focus
Bone Research at NYUCD: An Update


Dr. Nicola Partridge




The new bench laboratory in the Department of Basic Science and Craniofacial Biology.




Dr. Partridge and Dr. Despina Sitara examine images of a gel of DNA produced by the molecular imager in the Department of Basic Science and Craniofacial Biology's new equipment room.




Dr. Partridge and Dr. Xin Li in the new bench laboratory.




Dr. Partridge, right, Dr. Juhee Jeong, left foreground, and Dr. Xin Li, center, in the new tissue culture room.




When Dr. Nicola Partridge, an international authority on molecular endocrinology and bone and mineral research, arrived at NYUCD in the fall of 2009, she set out to develop synergies among bone researchers at NYUCD and at other institutions and to recruit additional basic science faculty to NYUCD, particularly in the area of bone biology. In the following conversation, Dr. Partridge provides an update on these activities.

Global Health Nexus (GHN): What is the focus of your current research activity?

Dr. Partridge: I am researching the action of parathyroid hormone, or PTH, in bone and mineralized tissue. PTH increases the concentration of calcium in the blood, enhancing the release of calcium from bone and indirectly stimulating osteoclasts, the cells responsible for bone resorption.

Recently, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded me a four-year, $1.3 million extension of a PTH research grant that the NIDDK has funded continuously since 1993. The new funding enables me to begin in vivo research on how PTH regulates repressor proteins known as histone deacetylases.

Repressors are DNA-binding proteins that prevent the transcription of genes. A better understanding of how parathyroid hormone regulates repressor proteins could contribute to the development of drugs that combat genetic disorders, and could help us learn about side effects caused by drugs that treat cancer by targeting the repressor proteins.

GHN: What advances have you made in recruiting junior research faculty to the Department of Basic Science and Craniofacial Biology?

Dr. Partridge: I recruited three new faculty members in 2010 with the help of a $1.5 million grant awarded by the National Institute of Dental and Craniofacial Research (NIDCR):

  • Dr. Despina Sitara, formerly a postdoctoral fellow in immunology and infectious diseases at the Harvard University School of Public Health, was hired in October 2010 as an assistant professor of basic science and craniofacial biology, and is currently studying a bone growth factor that has been linked to chronic renal failure—research that could help explain the process by which kidney failure may be linked to mineralization disorders, such as the mineralization of the aorta in cardiovascular disease.
  • Dr. Xin Li, formerly a research fellow in periodontics and oral medicine at the University of Michigan School of Dentistry, was hired in January 2011 as an assistant professor of basic science and craniofacial biology, and is conducting in vivo research on cancer metastasis to bone, and, in particular, why prostate cancer metastasizes so quickly to bone in diabetics.
  • Dr. Shoshana Yakar, currently an associate professor of endocrinology/diabetes and bone disease at the Mount Sinai School of Medicine, will be joining NYUCD in September 2011, as an associate professor of basic science and craniofacial biology. Dr. Yakar will focus initially on how insulin-like growth factors produced in the liver affect bone growth and the aging process.

A fourth researcher, Dr. Juhee Jeong, joined NYUCD in September 2010 as an assistant professor of basic science and craniofacial biology with postdoctoral research funding originally awarded to her in 2009 by the National Institute of Dental and Craniofacial Research (NIDCR) while she was in her previous position as a researcher in the Department of Psychiatry at the University of California, San Francisco. Dr. Jeong has begun the second, three-year phase of the grant, which involves studying transcription factors involved in palate development.

To accommodate the four new researchers, NYUCD has added a 2,400-square-foot laboratory to augment existing laboratory space for the Department of Basic Science and Craniofacial Biology. The new laboratory contains two faculty offices, a microscopy room, tissue culture room, equipment room, developer room, and four rows of bench laboratory space.

GHN: How have you expanded research collaborations both within NYUCD and between NYUCD and other institutions?

Dr. Partridge: In the past, an obstacle to collaboration was the lack of information sharing among 14 faculty members from nine academic departments within NYUCD and the NYU School of Medicine who are involved in bone research. When I arrived at NYUCD, one of the first steps I took was to initiate a monthly meeting at which faculty present their work and explore potential alliances.

Dr. Cristina Teixeira, associate professor of orthodontics and of basic science and craniofacial biology and interim chair of the Department of Orthodontics, leads the meetings, which draw faculty members from NYUCD's Departments of Basic Science and Cranio-facial Biology; Biomaterials and Biomimetics; Orthodontics; Periodontology and Implant Dentistry; Oral and Maxillofacial Pathology, Radiology and Medicine; and Prosthodontics; and the Departments of Orthopaedic Surgery; Medicine; and Microbiology at the NYU School of Medicine. Dr. Steven Abramson, codirector of the Center of Excellence on Musculoskeletal Disease at NYU, also regularly attends the meetings with his colleagues.

These meetings have led to a number of recent collaborative grant applications to the National Institutes of Health (NIH), including:

A proposal by Dr. Teixeira to the NIDCR for a study on cartilage and bone cell development, in which I will be a coinvestigator contributing my expertise on transcription factors regulating gene expression in cell development.

A proposal submitted jointly to the NIDCR by Dr. Kenneth Fleisher, assistant professor of oral and maxillofacial surgery, and Dr. Deepak Saxena, assistant professor of basic science and craniofacial biology, to research the development of osteonecrosis of the jaw (ONJ). Dr. Fleisher will coordinate the study; Dr. Saxena will focus on identifying bacteria that may contribute to disease onset; I will be a coinvestigator focusing on the impact of bisphosphonate drug use on bone cells; and a second coinvestigator, Dr. Zoya Kurago, assistant professor of oral and maxillofacial pathology, radiology and medicine, will study immune system changes that may be linked to ONJ progression.

I've also established a presence for NYUCD at faculty meetings of the Center of Excellence on Musculoskeletal Disease. Dr. Louis Terracio, NYUCD's Vice Dean for Research, Dr. Teixeira, and I attend the quarterly meetings, where we present updates on NYUCD research activity and learn about developments in musculoskeletal disease research at NYU.

Information sharing at these meetings has led to a number of recent collaborative grant applications to the NIH. For example, I recently submitted a proposal to the NIH's National Center for Research Resources for funding to enable NYUCD to acquire a micro computer tomography scanner in 2012 for use by over a dozen faculty members from NYUCD, the NYU Langone Medical Center, and the NYU Hospital for Joint Diseases.

The new scanner would supplement one that NYUCD acquired eight years ago, which is currently housed in the Department of Biomaterials and Biomimetics. The new machine will have a higher capacity than the older one, and will produce higher-resolution images. Its acquisition will enable the three institutions to better accommodate the growing needs of research faculty for high-resolution, three-dimensional images that illuminate the cellular development of teeth, bone, and cartilage.

The acquisition will also facilitate collaborations between the three institutions. For example, Dr. Teixeira and Dr. Abramson plan to use the new scanner to examine cellular changes to cartilage caused by osteoarthritis.

The new micro CT would be housed in NYUCD's Department of Orthodontics, whose faculty will use it to analyze molecular changes to teeth and underlying bone cells during the tooth movement process. Dr. Rodrigo Viecilli, assistant professor of orthodontics, will manage the machine and train faculty from the three institutions in its use, and Dr. Timothy Bromage, adjunct professor of biomaterials and biomimetics and of basic science and craniofacial biology, and an authority on 3D imaging, will contribute his expertise to a variety of studies that will utilize micro CT scanning.

Coinvestigators on this grant proposal include Dr. Bruce N. Cronstein, the Esserman Professor of Medicine and professor of pathology and pharmacology at the NYU School of Medicine; Dr. Abramson; Dr. Thorsten Kirsch, co-director of the Center of Excellence on Musculoskeletal Disease; and Dr. Claudio Basilico, chairman of the Department of Microbiology at the NYU School of Medicine.

I also recently submitted a grant application to the NYU Clinical and Translational Science Institute (CTSI) for a collaborative study with the NYU Hospital for Joint Diseases to investigate the process by which PTH injections stimulate bone formation. In an earlier study, bone formation was observed in rats and mice receiving daily injections of PTH. That research suggests that a chemokine regulated by PTH is involved in the increase in bone formation. The new grant application proposes to investigate the actions of this chemokine in 58 post-menopausal women receiving PTH injections. Multiple blood samples of the women would be taken over a four-hour period following PTH injection.

The research would be conducted at the Bellevue Hospital Center under the auspices of the NYU CTSI in collaboration with Dr. Stephen Honig, clinical associate professor of medicine and director of the Osteoporosis Center at the NYU Hospital for Joint Diseases, and Dr. Ann Danoff, associate professor and director of the Division of Endocrinology, Diabetes and Metabolism at the NYU School of Medicine.

GHN: What are your research goals going forward?

Dr. Partridge: A primary goal is to conduct more collaborative research involving the NYU Langone Medical Center, particularly in the area of transcription. I am also pursuing the possibility of developing a new center of excellence for craniofacial research and surgery that would be a collaborative venture between NYUCD's Departments of Basic Science and Craniofacial Biology; Oral and Maxillofacial Surgery; Biomaterials and Biomimetics; and the Institute of Reconstructive Plastic Surgery at the NYU Langone Medical Center.