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Vicki Huff, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Genetics, Division of Basic Science Research, UT M.D. Anderson Cancer Center, Houston, TX

Research Interests

  • Human genetics
  • Cancer genetics
  • Familial cancer predisposition
  • Kidney development

My research program focuses on identifying and understanding the normal function of genes whose alteration is a critical step during tumorigenesis. The model system I am using is Wilms tumor (WT), a childhood cancer of the kidney. One Wilms tumor gene, WT1, has been isolated, and we have identified germline and somatic mutations at this locus in roughly 20% of Wilms tumor cases. WT1 encodes a zinc finger transcription factor that is essential for normal embryonal development. Children heterozygous for germline WT1 mutations often display genitourinary anomalies and, depending upon the mutation, early onset renal failure.

We are investigating WT1 function in tumorigenesis and development using a combination of approaches, including mutational analysis of primary human tumors, development of mouse strains carrying WT1 mutations observed in humans and gene expression arrays. From this work we know that WT1 mutations are strongly associated with alteration of the wnt signaling pathway and that WT1 mutation results in a distinctive gene expression profile and loss of heterozygosity profile in tumors. We have generated a mutant mouse strain carrying a common missense mutation observed in WT patients (R394W) and have determined that heterozygous mutant mice develop early onset renal failure with a pathology and disease course identical to that in patients. We are now using this model to identify the early changes in gene expression that initiate the process of glomerulosclerosis and renal failure. We have also generated a mouse strain carrying a conditional knock-out Wt1 allele and are using this strain to investigate the role of Wt1 in the development and subsequent normal function of the kidney, ovaries and testes. Recently we have determined that ablation of Wt1 function in the committed testes results in complete loss of testes architecture, germ cells and Sertoli cells. Current experiments are now focused on understanding the molecular and cellular consequences of Wt1 ablation in the testes.

My laboratory has also determined that WT1 is not responsible for the Wilms tumor predisposition observed in most families, demonstrating that predisposition to Wilms tumor is genetically heterogeneous. We have successfully localized to chromosome 19q the gene (FWT2) responsible for inherited predisposition to Wilms tumor in many families and are now sublocalizing it with the goals of isolating the gene, elucidating its role in normal and tumor development and understanding its role in tumorigenesis. Overall, these studies will help to elucidate the genes and cellular pathways critical for the regulation of cell growth and differentiation in normal kidney and how those functions are abrogated during tumorigenesis.

Office Address

Phone: (713) 834-6384
Email: vhuff@mdacc.tmc.edu

Education & Training

Degree-Granting Education

1987 University of Michigan, Ann Arbor, MI, PHD, Human Genetics

Selected Publications

Peer-Reviewed Original Research Articles
1. Gao F, Maiti S, Alam N, Zhang Z, Deng JM, Behringer RR, Lecureuil C, Guillou F, Huff V. The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A 103(32):11987-92, 8/2006. e-Pub 7/28/2006. PMCID: PMC1567685.
2. Ruteshouser EC, Hendrickson BW, Colella S, Krahe R, Pinto L, Huff V. Genome-wide loss of heterozygosity analysis of WT1-wild-type and WT1-mutant Wilms tumors. Genes Chromosomes Cancer 43(2):172-80, 6/2005. PMID: 15761866.
3. Gao F, Maiti S, Sun G, Ordonez NG, Udtha M, Deng JM, Behringer RR, Huff V. The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. Mol Cell Biol 24(22):9899-910, 11/2004. PMID: 15509792.
4. Ruteshouser EC, Huff V. Familial Wilms tumor. Am J Med Genet C Semin Med Genet 129(1):29-34, 8/2004. PMID: 15264270.
5. Royer-Pokora B, Beier M, Henzler M, Alam R, Schumacher V, Weirich A, Huff V. Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am J Med Genet A 127(3):249-57, 6/2004. PMID: 15150775.
6. Udtha M, Lee SJ, Alam R, Coombes K, Huff V. Upregulation of c-MYC in WT1-mutant tumors: assessment of WT1 putative transcriptional targets using cDNA microarray expression profiling of genetically defined Wilms' tumors. Oncogene 22(24):3821-6, 6/2003. PMID: 12802290.

Last updated: 9/15/2009