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Endocrine Neoplasia Laboratory

Photo of James Koh, PhD

James Koh, PhD

Office: Room B217 LSRC, 308 Research Drive, Durham, NC 27710
Campus Mail: Box 3873 DUMC, Durham, NC 27710
Phone: 919-684-0892
Fax: 
919-681-6622

Scientific Focus


Parathyroid oxyphil cells (green) within a parathyroid adenoma

In collaboration with Dr. Julie Sosa, the Endocrine Neoplasia Laboratory employs a combination of molecular, murine modeling, and live-cell imaging approaches to examine the underlying mechanisms of disrupted calcium sensing in parathyroid tumors. Our group has shown recently that parathyroid adenomas are comprised of functionally discrete and separable cellular subpopulations that respond differentially to extracellular calcium stimulation and that arise in many cases following polyclonal expansion of progenitor cells within the parathyroid gland.

To examine cell-signaling behaviors in the native context of viable tumor tissue, we have developed a novel ex vivo imaging system that enables direct provocative testing of tumor reactivity to physiological agonist engagement at single-cell resolution. These methods form the foundation for our laboratory’s ongoing efforts to understand how perturbed biochemical signaling can contribute to the development of preneoplastic lesions in human endocrine neoplasia.

  • Ex vivo analysis of biochemical signaling in human parathyroid tissue
  • High-throughput image-based quantitative metrics of live cell signaling
  • Development of live-cell microfluidic imaging platforms for functional interrogation of tumor cell behaviors

  • Molecular determinants of calcium sensing deficiency in parathyroid disease

Selected Achievements


Isolation of distinct cellular subtypes from a parathyroid adenoma. Background image=immunofluorescence. Foreground image=flow cytometry sorting of tumor cells. Inset=electron microscope images of parathyroid tumor cell types isolated by flow cytometry

Our group has developed a series of novel image-based approaches for visualizing the functional consequences of intratumoral heterogeneity within living human tumor specimens. We have shown recently that human parathyroid tumors are comprised of functionally discrete and separable cellular subpopulations that respond differentially to extracellular calcium stimulation and that arise in many cases following polyclonal expansion of progenitor cells within the parathyroid gland. We are employing a combination of live single-cell dynamic calcium response imaging at both the single-cell and intact tissue level, in combination with transgenic mouse modeling to study how these newly identified cellular subpopulations drive the failure of appropriate calcium sensing in parathyroid disease.

Dr. Julie Sosa and I are MPIs on an active R21 proposal that utilizes a novel live-cell microraft system that we developed to investigate the molecular determinants of parathyroid cell calcium responsiveness at the single-cell level.

In addition, our group has developed immunofluorescence-based and flow cytometric approaches for studying signaling events, cellular proliferation, and oncoprotein-mediated transformation in addition to extensive prior work on transcriptional regulation and promoter occupancy. Our laboratory is currently partnering with Cell Microsystems, Inc., in the development of a high-performance optical imaging device for stand-alone live-cell imaging at subcellular resolution. 


Overlay of live-cell calcium responsiveness readout (green) and parathyroid hormone expression (red) in a living human parathyroid tumor section

In collaboration with Dr. John Olson of the University of Maryland, we have shown that aberrant overexpression of a potent regulator of G-protein signaling is a mechanism for inhibiting cellular responsiveness to calcium sensing both in vitro and in vivo in RGS5-deficient mice, and we recently completed an R01 project dedicated to elucidating the role of this regulator (RGS5) in parathyroid disease in a novel transgenic mouse model. As part of this work, we generated a new transgenic strain engineered for conditional, tissue-specific expression of RGS5 in the parathyroid gland.

Contact Us

Please feel free to contact the laboratory or come by for a visit:

James Koh, PhD
Tel: 919-684-0892
Email: james.koh@duke.edu
Office: Room B217 LSRC
Laboratory: Room B215 LSRC

Latest Publications

Shi, Y, Azimzadeh, P, Jamingal, S, Wentworth, S, Ferlitch, J, Koh, J, Balenga, N, and Olson, JA. "Polyclonal origin of parathyroid tumors is common and is associated with multiple gland disease in primary hyperparathyroidism." Surgery 163, no. 1 (January 2018): 9-14.

Full Text

Koh, J, Hogue, JA, and Sosa, JA. "Live-Cell Visualization of Calcium Flux in Vibratome-Cut Thick Sections of Viable Tumor Tissue." Current protocols in cell biology 77 (December 11, 2017): 4.34.1-4.34.16.

Full Text

Weber, TJ, Koh, J, Thomas, SM, Hogue, JA, Scheri, RP, Roman, SA, and Sosa, JA. "Impaired calcium sensing distinguishes primary hyperparathyroidism (PHPT) patients with low bone mineral density." Metabolism: clinical and experimental 74 (September 2017): 22-31.

Full Text

Balenga, N, Azimzadeh, P, Hogue, JA, Staats, PN, Shi, Y, Koh, J, Dressman, H, and Olson, JA. "Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling." Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32, no. 3 (March 2017): 654-666.

Full Text