Giampero (John) A Martignetti, MD, PhD Email Giampero (John) Martignetti
- PROFESSOR | Genetics and Genomic Sciences
- PROFESSOR | Oncological Sciences
- PROFESSOR | Obstetrics, Gynecology and Reproductive Science
- PROFESSOR | Pediatrics
- Genetics and Genomics
- Hospital Affiliation
- The Mount Sinai Hospital
- Department of Human Genetics 212-659-6744212-659-6744
Cancer Genetics, Gene Discovery, Genomics, Molecular Biology, Tumor Suppressor Genes
Multi-Disciplinary Training Areas
Cancer Biology [CAB], Genetics and Data Science [GDS], Pharmacology and Therapeutics Discovery [PTD]
BA, Columbia College
MPhil, Cambridge University
MD, PhD, Mount Sinai School of Medicine
MD, Mount Sinai Sch. of Medicine CUNY
Mount Sinai Hospital
Fellowship, Human Genetics
Mount Sinai Hospital
English, Italian, Spanish
The translational research in our laboratory focuses on four major human disease themes: 1. Osteolysis and arthritis; 2. Cancer genetics and cancer syndromes; 3. Metabolic and genetic basis of obesity, and; 4. Hereditary platelet disorders. In each, combinations of genetic, biochemical, genomic, proteomic and model system approaches are used to explore the molecular basis of the disease and then, ultimately, target diagnostic and treatment strategies for patients with these disorders. In collaboration with other clinical and basic science researchers, and across these human diseases, we have used this approach to define novel human syndromes and disease genes and then use these discoveries to understand the biologic basis of the underlying physiology and pathophysiology.
Two examples of current studies are provided. We first characterized and described with colleagues a severe osteolysis and arthritis syndrome [Am J Med Genet. 93:11-18; 2000]. Using a positional cloning strategy, we then localized and identified that the disease was caused by inactivating mutations in the matrix metalloproteinase 2 gene (MMP-2); the first identified MMP deficiency [Nat Genet 28:261-5; 2001]. Counterintuitively, MMP-2 is a member of the matrix metalloproteinase family of proteolytic enzymes which degrade the extracellular matrix (ECM) during tissue remodeling and are involved in various critical cellular processes including cell migration, proliferation, and apoptosis. The overall goal of current ongoing patient, mouse model and biochemical studies is to resolve the apparent paradox created by our original findings in affected individuals: "How does functional loss of a single proteolytic enzyme result in increased bone loss and joint destruction".
A second example is provided by studies in human cancer. We originally demonstrated, in collaboration with Dr. Scott Friedman's laboratory, that KLF6, a member of the Kruppel-like family of zinc finger transcription factors which regulate growth-related signal transduction pathways, mediates growth suppression by a p53-independent, upregulation of p21 and is a tumor suppressor gene [Science 294:2563-6; 2001; Am J Pathol 162:1047-52; 2003]. We have now further demonstrated loss or inactivation of KLF6 in a number of major human cancers including ovarian cancer [Clin Cancer Res. 12:3730-9; 2006], colorectal cancer [Gastroenterology 126:1090-103; 2004], hepatocellular carcinoma [Hepatology. 40:1047-52; 2004], head and neck squamous cell carcinoma [In Press, 2007], and malignant glioma [In Press, 2007].
Beyond this, we recently demonstrated in a multicenter, prostate cancer study of greater than 3,400 men that a prevalent KLF6 germline single nucleotide polymorphism (SNP) is associated with an increased lifetime cancer risk [Cancer Res. 65:1213-22; 2005]. The SNP results in the increased transcription of an alternatively spliced, biologically active KLF6 isoform [Cancer Res. 65:5761-8; 2005]. We are now investigating the co-opted, critical pro-survival functions of KLF6-SV1 in patient samples and genetically engineered tumor cells and mouse and drosophila models and exploring the role of targeted KLF6-SV1 silencing as a potential therapeutic agent in human cancers.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Martignetti during 2018 and/or 2019. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Other activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership
- Karyopharm Inc.
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