Research Centers

Neuroendocrine Malignancies Clinical Research

The Neuroendocrine Center is one of the premier multidisciplinary clinical and research programs in neuroendocrinology and pituitary tumors in the USA. A recognized international referral center, the Neuroendocrine Center incorporates multidisciplinary expertise from Neuroendocrinology, Neurosurgery, Neurology, Radiation Oncology and Psychiatry.

Neuroendocrine Malignancies Investigators Anne Klibanski, MD
Beverly M.K. Biller, MD
Thomas N. Byrne, MD
Steven K. Grinspoon, MD
Janet Lo, MD
Jay S. Loeffler, MD
Robert L. Martuza, MD
Karen K. Miller, MD
Madhusmita Misra, MD
Lisa B. Nachtigall, MD

George Papakostas, MD
Steve J. Russell, MD, PhD
Helen A. Shih, MD, MS
Brooke Swearingen, MD
Melissa K. Thomas, MD, PhD
Andrea L. Utz, MD, PhD

Research Summary

Our overall research mission is to investigate the:

  • Pathogenesis and regulation of human pituitary adenomas
  • Pathophysiology of neuroendocrine disorders
  • Relationship between nutritional disorders and neuroendocrine factors
  • Development of novel therapies for patients with pituitary and hypothalamic disorders.

Our clinical mission is to advance the diagnosis and treatment of patients with pituitary and neuroendocrine disorders. The Neuroendocrine Center is an internationally recognized research center in neuroendocrinology and pituitary disease. Investigators in the Center have been awarded 14 NIH and federal research grants. In addition, funding from industry and private foundations includes the awarding of one of six Global Endocrinology and Metabolism (GEM Centers) for investigator initiated research by Pharmacia; investigator initiated grants from Novartis to study somatostatin receptor subtypes and pituitary tumors; and participation in international clinical research studies. Research in the Neuroendocrine Center incorporates both clinical and translational laboratory investigations in neuroendocrinology. Parallel in vitro and in vivo investigations have allowed the more basic studies of pituitary tumor pathogenesis and regulation to be brought directly into the clinical research arena. Investigators in the Neuroendocrine Center have played key leadership roles in the establishment and implementation of nationally recognized research programs in neuroendocrine disorders. Investigators have pioneered novel therapies for patients with secretory pituitary tumors, including the use of GH receptor antagonists and somatostatin receptor subtype specific analogues.

Another major focus of research is the relationship between the neuroendocrine axis and body composition. In recent collaborative work with the bioimaging groups in psychiatry and radiology, we are investigating the impact of psychiatric disorders and associated hormone disorders on specific brain regions, and the use of novel imaging modalities to investigate the effects of hormone deficiency states on body composition. Of major importance is the continued 20-year collaboration between Dr. Klibanski and the Neurosurgical Service on ongoing grants investigating pituitary tumorigenesis.

Another key ongoing collaboration exists with the Department of Radiation Oncology. This has resulted in improved patient care for patients following cranial irradiation, and publications regarding the effects of radiotherapy on hypothalamic/pituitary function. The creation and expansion of the Neuroendocrine Center has provided a patient base for obtaining tumor tissue for in vitro experiments, conducting clinical studies, as well as providing continued excellent care to these patients.

Molecular Pathogenesis of Human Pituitary and Benign Brain Tumors

Pituitary tumors are the most common CNS tumor. Research highlights include:

  • The finding of dominant negative tumor specific mRNAs encoding activin/TGFß receptors in human pituitary tumors, which may promote cell growth
  • The role of somatostatin receptor subtypes in regulating hormone and proliferation in human pituitary adenomas
  • The identification and role of novel tumor suppressor genes in pituitary tumor and brain tumor pathogenesis

Novel Therapies for Pituitary Tumors

Research highlights include:

  • The effects of a GH receptor antagonist to decrease IGF-1 and GH action in patients with acromegaly
  • The use of specific somatostatin receptor analogues in the treatment of acromegaly and Cushing's syndrome
  • Identification of MEG3, an imprinted gene that functions as a non-coding RNA to suppress tumor growth

1 Swearingen B, Katznelson L, Miller K, Grinspoon S, Waltman A, Dorer DJ, Klibanski A, Biller BM
Diagnostic errors after inferior petrosal sinus sampling.
J Clin Endocrinol Metab. 08/04/2004; 89(8); 3752-63.

 

2 Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A
Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors.
J Clin Endocrinol Metab. 04/07/2005; 90(4); 2179-86.

 

3 Melmed S, Sternberg R, Cook D, Klibanski A, Chanson P, Bonert V, Vance ML, Rhew D, Kleinberg D, Barkan A
A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly.
J Clin Endocrinol Metab. 07/08/2005; 90(7); 4405-10.

 

4 Miller KK, Biller BM, Beauregard C, Lipman JG, Jones J, Schoenfeld D, Sherman JC, Swearingen B, Loeffler J, Klibanski A
Effects of testosterone replacement in androgen-deficient women with hypopituitarism: a randomized, double-blind, placebo-controlled study.
J Clin Endocrinol Metab. 05/08/2006; 91(5); 1683-90.

 

5 Batista DL, Zhang X, Gejman R, Ansell PJ, Zhou Y, Johnson SA, Swearingen B, Hedley-Whyte ET, Stratakis CA, Klibanski A
The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.
J Clin Endocrinol Metab. 11/07/2006; 91(11); 4482-8.

 

6 Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A
Activation of p53 by MEG3 non-coding RNA.
J Biol Chem. 08/20/2007; 282(34); 24731-42.

 

7 Petit JH, Biller BM, Yock TI, Swearingen B, Coen JJ, Chapman P, Ancukiewicz M, Bussiere M, Klibanski A, Loeffler JS
Proton Stereotactic Radiotherapy for Persistent ACTH-Producing Adenomas.
J Clin Endocrinol Metab. 11/21/2007;

 

8 Shih HA, Loeffler JS
Radiation therapy in acromegaly.
Rev Endocr Metab Disord. 12/17/2007;

 

9 Petit JH, Biller BM, Coen JJ, Swearingen B, Ancukiewicz M, Bussiere M, Chapman P, Klibanski A, Loeffler JS
Proton stereotactic radiosurgery in management of persistent acromegaly.
Endocr Pract. 01/15/2008; 13(7); 726-34.