- PROFESSOR | Genetics and Genomic Sciences
- PROFESSOR | Pediatrics
- Clinical Genetics - MD
- Hospital Affiliations
- The Mount Sinai Hospital
- Mount Sinai Beth Israel
- Biotinidase Deficiency
- Carnitine Disorders
- Disorders Of Cobalamin Metabolism
- Disorders Of Tetrahydrobiopterin Metabolism
- Fatty Acid Oxidation Defects
- Glutaric Acidemia
- Glycogen Storage Diseases
- Intellectual Disability
- Krabbe Disease
- Maple Syrup Urine Disease
- Metabolic Encephalopathy
- Methylmalonic Acidemia
- Mitochondrial Myopathy
- Newborn Screening
- Organic Acidemias
- Pompe Disease
- Propionic Acidemia
- Urea Cycle Defects
Chemokines, Chemotaxis, Genetics, Genomics, Human Genetics and Genetic Disorders, Immunology, Microtubules, Signal Transduction, Virulence Genes
Multi-Disciplinary Training Areas
Clinical Research Education Program [CLR], Genetics and Genomic Sciences [GGS], Immunology [IMM]
MD, S.U.N.Y., Health Science Center
Mount Sinai Hospital
Fellowship, Human Genetics
Mount Sinai Hospital
Chemokine mutations in WHIM syndrome
WHIM syndrome is a rare immunodeficiency causing hypogammaglobulinemia, neutropenia and predisposition to warts. Affected individuals have been found to carry truncating mutations in the tail domain of the CXCR4 chemokine receptor. The pathogenesis of the disease appears to involve both a neutrophil trafficking defect as well as a defect in lymphocyte function. While the nature of the susceptibility to HPV is poorly understood, additional study should provide insight into the role of the receptor in the host response to infection by HPV, a cause of significant human morbidity. Studies currently underway include the characterization of a mouse model expressing mutant CXCR4 in selected hematopoietic tissues, genetic studies with functional candidate genes in families with the WHIM syndrome phenotype without mutations in CXCR4, and biochemical characterization of the signaling perturbations in disease cells carrying CXCR4 truncations.
Disease Gene Discovery and Translational Genomics
The Diaz laboratory studies the molecular basis of inherited human diseases, particularly single-gene disorders. Methodologies applied within the laboratory include linkage analysis, positional cloning, development of animal models and elucidation of disease pathophysiology through biochemical and cell biological studies. By understanding the underlying pathobiology of these disorders, fundamental insights can be gained into more broadly relevant biological or clinical questions.
Tubulin folding defects in human disease
Mutation of a tubulin-specific chaperone protein, TBCE, has been found to cause autosomal recessive Kenny-Caffey syndrome (KCS), a dwarfing syndrome associated with congenital hypoparathyroidism and mental retardation. A spontaneous mutant of the orthologous mouse gene, Tbce, was identified by other investigators in a murine model of peripheral motor neurodegeneration (pmn), implicating the chaperone in maintenance of the microtubule cytoskeleton in motor axons. Biochemical studies have confirmed that the disease pathophysiology is not caused by loss of tubulin folding function, suggesting a novel role for the protein. Interaction with a microtubule growth regulator, EB1 has been demonstrated, consistent with a role for TBCE in the organization of microtubules. Current work is focused on validating this proposed function and exploring the role of TBCE in maintaining microtubule stability. Defects in microtubule stability in neuronal cells appears to be a potential common pathogenic pathway disturbed in several neurodegenerative disorders, suggesting TBCE and its interactors as potential modifiers.
An Open Label Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate (GPB; RAVICTI®) in Pediatric Subjects under Two Years of Age with Urea Cycle Disorders (UCDs)
The purpose of this study is to evaluate the safety of RAVICTI in patients less than 2 years of age, to determine RAVICTI’s ability to manage UCD (Urea Cycle Disorders) in patients less than 2 years of age, and to evaluate drug blood levels of RAVICTI in patients less than 2 year...
A Phase 1 Open-label, Dose-escalation Study of AEB1102 in Patients with Arginase I Deficiency and Hyperargininemia
This is a Phase 1, single-arm, open-label, dose-escalation study of AEB1102 (Co-ArgI-PEG) in up to 6 adult patients with arginase I deficiency and hyperargininemia. Each patient will receive a maximum of 4 doses (one injection at each of 4 dose levels) of AEB1102 with a two-week ...
A Phase 3 Randomized Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sialic Acid Extended-Release Tablets in Patients with GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
The purpose of this study is to measure the potential effects of an experimental drug, Sialic Acid-Extended Release (SA-ER) tablets, compared to placebo tablets. SA-ER tablets are in development as a treatment for GNE Myopathy but are not approved by the US Food and Drug Administ...
Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
The purpose of this study is to see if a new drug, Carbaglu (N-carbamylglutamate, NCG) reduces blood ammonia levels and whether it helps to protect the brain in propionic acidemia, methylmalonic acidemia, carbamylphosphate synthetase I deficiency, or ornithine transcarbamylase de...
Molecular & Enzymatic Inherited Metabolic Diseases
The purpose of this project is to study urine and blood samples to identify substances that will help doctors to better understand inherited metabolic diseases.
Tian G, Huang MC, Cowan NJ, Diaz GA, Parvari R. Cryptic out-of frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD. Proc Nat Acad Sci USA 2006; 103: 13491-13496.
Diaz GA. CXCR4 mutations in WHIM syndrome: a misguided immune system? [review]. Imm Reviews 2005; 203: 235-243.
Oishi K, Diaz GA, Gelb BD, Barchi M. Male infertility due to germ cell apoptosis in mice lacking the thiamin carrier, Tht1. A new insight into the critical role of thiamin in spermatogenesis. Devel Biol 2004; 266: 299-309.
Hernandez PA, Gorlin RJ, Lukens JN, Diaz GA, Francois F, Klotman ME, Bohinjec J. Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nature Genetics 2003; 34: 70-74.
. Mutation of TBCE causes the hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome. Nature Genetics 2002; 32: 448-452.
Snyderman S, Diaz GA, Sansiricq C, Wasserstein M, Kornreich M, Edelmann L. Maple Syrup Urine Disease: Identification and carrier frequency determination of a novel founder mutation in the Ashkenazi Jewish population. Am J Hum Genet 2001; 69: 863-868.
Diaz GA, Gelb BD, Risch N, Nygaard TG, Frisch A, Cohen I, Desnick RJ, Amaral O, Maire I, Poenaru L, Caillaud C, Weizberg M, Mistry P, Sa Miranda C. Gaucher Disease: The origins of the Ashkenazi Jewish N370S and 84GG mutations. Am J Hum Genet 2000; 66: 1821-1832.
Diaz GA, Banikazemi M, Gelb BD, Jalali M, Desnick RJ, Vossough P. Mutations in a new gene encoding a thiamine transporter cause the thiamine-responsive megaloblastic anaemia syndrome. Nature Genetics 1999; 22: 309-312.
Diaz GA, Gelb BD, Khan KS. The autosomal recessive Kenny-Caffey syndrome locus maps to chromosome. Genomics 1998; 54: 13-18.
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. Diaz during 2016 and/or 2017. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
- BioMarin Pharmaceutical Inc.
- Gerson Lehrman Group
Other activities: Examples include, but are not limited to, committee participation, data safety monitoring board (DSMB) membership
- Hyperion Therapeutics
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.
Physicians who provide services at hospitals and facilities in the Mount Sinai Health System might not participate in the same health plans as those Mount Sinai hospitals and facilities (even if the physicians are employed or contracted by those hospitals or facilities).
Information regarding insurance participation and billing by this physician may be found on this page, and can also be obtained by contacting this provider directly. Because physicians insurance participation can change, the insurance information on this page may not always be up-to-date. Please contact this physician directly to obtain the most up-to-date insurance information.
Insurance and health plan networks that the various Mount Sinai Health System hospitals and facilities participate in can be found on the Mount Sinai Health System website.