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Faculty Sanjay M. Mallya
Assistant Professor of Oral Health and Diagnostic Sciences, Division
of Oral Diagnosis
mallya@nso2.uchc.edu
Areas of Interest:
The major focus of my laboratory is the study of the molecular
mechanisms of oral neoplastic progression. Using transgenic animal
models of oral premalignancy, we are studying the interaction between
genetic and environmental factors in the development of oral squamous
cell carcinoma, and the molecular and genetic events that occur during
the multi-step progression of these neoplasms.
A second area of research is the mechanisms that underlie the effects
of parathyroid hormone on bone. It is well established that PTH has both
catabolic and anabolic effects on bone. However, the molecular bases for
these effects are poorly understood. To better understand the mechanisms
that underlie these differential effects of PTH, we have embarked on
studies using a transgenic mouse model of hyperparathyroidism. We are
presently investigating the effects of PTH excess on cancellous and
cortical bone mass architecture using molecular, histomorphometric and
imaging-based approaches.
Lab Rotation Projects:
1. Molecular and genetic events in the development of oral epithelial
dysplasia and neoplasia.
Using a transgenic animal model, where tissue-specific overexpression
of cyclin D1 drives oral epithelial dysplasia, we are studying the role
of p16 and EGFR in the process of oral carcinogenesis.
2. Characterization of a mouse model for somatic gene delivery to
oral keratinocytes.
We have recently developed a novel mouse model for somatic gene
delivery to the oral keratinocytes. We are presently optimizing the use
of this model to study the process of oral carcinogenesis.
3. Role of the cyclin D1 pathway in oral carcinogenesis.
Using animal models and cell culture systems, we are dissecting the
regulation and role of the cyclin D1 pathway in regulating keratinocytes
proliferation.
4. Effect of parathyroid hormone excess on the skeleton
Using a transgenic mouse model of hyperparathyroidism, we are
studying the skeletal changes that occur in the cancellous and cortical
compartments of bone, and the cellular changes that underlie these
effects, using histological, histomorphometric and imaging-based
approaches.
5. Molecular pathogenesis of fibro-osseous lesions of the jaws
Fibro-osseous lesions of the jaws are a diverse group of lesions
characterized by replacement of normal bone with a fibroblastic stroma
and abnormal bone/cementum. We are analyzing these lesions for mutations
in specific genes that may contribute to their pathogenesis.
Selected Publications:
Mallya SM, Gallagher JJ and Arnold A. Analysis of microsatellite
instability in sporadic parathyroid adenomas. Journal of Clinical
Endocrinology and Metabolism, 88 (3): 1248-1251, 2003.
Imanishi Y, Hosokawa Y, Yoshimoto K, Schipani E, Mallya S,
Papanikolaou A, Kifor O, Tokura, T, Sablosky M, Ledgard F, Gronowicz G,
Wang TC, Schmidt EV, Hall C, Brown EM, Bronson R and Arnold A. Primary
hyperparathyroidism caused by parathyroid-targeted overexpression of
cyclin D1 in transgenic mice. Journal of Clinical Investigation, 107
(9): 1093-1102, 2001.
Mallya SM and Arnold A. Cyclin D1 in parathyroid disease. Frontiers
in Bioscience. 5:D367-D371, 2000.
Arnold A, Shattuck TM, Mallya SM, Krebs LJ, Costa J, Gallagher J,
Wild Y and Saucier K. Molecular pathogenesis of primary
hyperparathyroidism. Journal of bone and mineral research, 17 Suppl
2:N30-6, 2002.
Shattuck TM, Mallya SM and Arnold A. Molecular genetic abnormalities
in sporadic primary hyperparathyroidism. In "Parathyroid Hormone
Molecular Biology", Ed: Tally Naveh. In press, Landes Bioscience.
Wang Y, Mallya SM and Sikpi MO. Calmodulin antagonists and cyclic AMP
inhibit ionizing-radiation-enhancement of double-strand-break repair in
human cells. Mutation Research, 460 (1), 29-39, 2000.
oshimoto K, Bernstein M, Wang TC, Schmidt EV, Arnold A. In vivo analysis
of mammary and non-mammary tumorigenesis in MMTV-cyclin D1 transgenic
mice deficient in p53. Transgenic Res 2001 10:471-478
Imanishi Y, Tahara H, Palanisamy N, Spitalny S, Salusky IB, Goodman
W, Brandi ML, Drueke TB, Sarafati E, Urena P, Chaganti RSK, Arnold A.
Clonal chromosomal defects in the molecular pathogenesis of refractory
hyperparathyroidism of uremia. J Amer Soc Nephrol 2002 in press. |
