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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Rizwan  Hamid

Rizwan Hamid, M.D., Ph.D.

Associate Professor of Pediatrics
Assistant Professor of Cancer Biology
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
1161 21st Ave. South
Nashville, TN 37232-2578
615-322-7601

Education

  • M.D., Allama Iqbal Med College Univ of Punjab Pakistan
  • Ph.D., Vanderbilt University
  • Clinical Fellow in Genetics, Vanderbilt University
  • Resident in Pediatrics, University of Miami/Jackson Memorial Hospital
  • Senior Resident in Pediatrics, University of Miami/Jackson Memorial Hospital

Research Description

Role of TGIF in Acute Myelogenous Leukemia (AML). We have discovered that quantitative expression of the stem cell expressed transcriptional repressor TGIF is the most discriminating and powerful predictor of patient survival identified in AML. Patients whose leukemic cells expressed decreased levels of TGIF RNA had a mean survival of 12 months, while patients whose leukemic cells expressed TGIF at a higher level had a mean survival of 60 months (p=0.00001).

Our data thus define a clinical role for TGIF as a prognostic indicator in AML, a role that has immediate clinical implications for AML treatment. Better risk stratification of AML patients, who prior to TGIF�s identification as a prognostic indicator did not have a usable prognostic indicator, will lead to better treatment decisions, with direct impact on morbidity and mortality. For example, in patients with high TGIF levels (expected to do well) stem cell transplant (SCT) would not be considered as an initial option, while in patients with low TGIF levels (expected to do worse), SCT would be an initial treatment option.

Our data also suggest a biological mechanism whereby TGIF affects AML prognosis. Our data show that Tgif may alter the exquisite balance between the key HSC functions of quiescence, self-renewal and differentiation. Regulation of these HSC functions is poorly understood and is frequently altered in acute leukemias; for example, increased quiescence in HSCs can make them more resistant to myelotoxic injury following chemotherapy, increasing the likelihood of relapse and/or poor long-term survival. Thus, elucidating the mechanisms through which Tgif alters HSC function will increase not only our understanding of HSC biology but also our comprehension of leukemia pathogenesis and treatment. Treatments that increase TGIF expression will make leukemic stem cells less quiescent and thus more likely to be affected by cytotoxic chemotherapy.

The research focus of this project is thus to

a) Understand and further define the cellular and molecular basis of Tgif�s role in normal and leukemic HSC function using mouse models.

b) Gain a better understanding of TGIF transcriptional pathway by identify downstream TGIF targets in HSC and use genetic and genomics approaches to identify genes and genomic regions that regulate TGIF expression.

c) Study the effects of single nucleotide polymorphisms (SNPs) on TGIF function and thus leukemic cell biology. There is a growing body of evidence that suggests that genetic factors play an important role in complex disease including cancer and that disease progression is determined by a complex interaction between somatic mutations and inherited traits. These inherited traits are usually SNPs or variants, and as opposed to a somatic mutation, these changes usually do not disrupt the gene function/expression but rather modify it. These variations would then impact the pathogenesis of a cancer by affecting its progression, metastasis, response to treatment and long-term survival. The role these common inherited variations play in leukemia biology has not been significantly explored. Our lab is in the process of addressing this important, but inadequately explored, aspect of leukemia pathogenesis.

Role of BMPR2 in Pulmonary Arterial Hypertension (PAH)

The long-term objectives of this project are to better understand the genetic factors that play a role in the pathogenesis of PAH and to use that information to improve disease diagnosis and therapy. More than 500,000 individuals are hospitalized annually in the United States with some form of PAH, and the mortality and morbidity increases each year. We have studied heritable (H) PAH, which is caused by mutations in the bone morphogenic protein-receptor-2 (BMPR2) gene, as a means to better understand the role of genetic risk factors involved in primary and secondary PAH.

Many key issues about HPAH remain unresolved, e.g., the mechanisms behind reduced penetrance, t

Clinical Interest

In my clinical practice, located in the Monroe Carell Jr. Children's Hospital, I evaluate both pediatric and adult patients. I manage all aspects of clinical genetics including

1. Cancer Genetics (including but not limited to breast cancer, colon cancer, thyroid cancer, and various genetic cancer syndromes).
2. Dysmorphic syndromes (such as Down syndrome, DiGeorge syndrome, Achondroplasia, Beckwith Wiedemann syndrome, Prader Willi syndrome, Angelman syndrome, Fragile X syndrome).
3. Metabolic disorders (including but not limited to propionic academia, PKU, galactosemia, methylmelonic academia, mitochondrial disorders and lysosomal storage diseases). Neurogenetics disorders (including but not limited to tuberous sclerosis, huntington�s disease, neurofibromatosis type I and II),
4. Adult genetic disorders (including but not limited to marfan�s syndrome, adult cancer counseling, Huntington�s disease, adult metabolic disease and NF1 and II).
5. Evaluation of autistic children.
6. Prenatal diagnosis/counseling.

Publications