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Vicki Huff, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX

Dual/Joint/Adjunct Appointment

Professor, The University of Texas Graduate School of Biomedical Sciences, Houston, TX

Research Interests

  • Human disease genetics
  • Cancer genetics
  • Familial cancer predisposition
  • Kidney and liver development
  • Mouse models for kidney and liver cancer

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.

 View a complete list of Dr. Huff's publications.

Office Address

The University of Texas MD Anderson Cancer Center
Department of Genetics Unit 1010
1515 Holcombe Blvd.
Houston, TX 77030
Room Number: S15.8316A
Phone: (713) 834-6384
Email: vhuff@mdacc.tmc.edu

Education & Training

Degree-Granting Education

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

Postgraduate Training

2/1987-2/1990 Postdoctoral Fellowship, Biochem & Mol Biol, The University of Texas MD Anderson Cancer Center, Houston, TX, Dr. Grady Saunders

Selected Publications

Peer-Reviewed Original Research Articles

1. Huang L, Mokkapati S, Hu Q, Ruteshouser EC, Hicks MJ, Huff V. Nephron progenitors but not stromal progenitor cells give rise to Wilms tumors in mouse models with β-catenin activation or Wt1 ablation and Igf2 upregulation. Neoplasia. In Press.
2. Palculict TB, Ruteshouser EC, Fan Y, Wang W, Strong L, Huff V. Identification of germline DICER1 mutations and loss of heterozygosity in familial Wilms tumour. J Med Genet. 11/2015. PMID: 26566882.
3. Walz AL, Ooms A, Gadd S, Gerhard DS, Smith MA, Guidry Auvil JM, Meerzaman D, Chen QR, Hsu CH, Yan C, Nguyen C, Hu Y, Bowlby R, Brooks D, Ma Y, Mungall AJ, Moore RA, Schein J, Marra MA, Huff V, Dome JS, Chi YY, Mullighan CG, Ma J, Wheeler DA, Hampton OA, Jafari N, Ross N, Gastier-Foster JM, Perlman EJ. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology wilms tumors. Cancer Cell 27(2):286-97, 2/2015. PMID: 25670082.
4. Mokkapati S, Niopek K, Huang L, Cunniff KJ, Ruteshouser EC, deCaestecker M, Finegold MJ, Huff V. β-Catenin Activation in a Novel Liver Progenitor Cell Type Is Sufficient to Cause Hepatocellular Carcinoma and Hepatoblastoma. Cancer Res 74(16):4515-25, 8/2014. e-Pub 5/2014. PMCID: PMC4134699.
5. Huff V. Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene. Nat Rev Cancer 11(2):111-21, 2/2011. e-Pub 1/2011. PMID: 21248786.
6. Hu Q, Gao F, Tian W, Ruteshouser EC, Wang Y, Lazar A, Stewart J, Strong LC, Behringer RR, Huff V. Wt1 ablation and Igf2-Up-regulation in mice result in Wilms tumors with elevated pERK1/2. J Clin Invest 121(1):174-83, 1/2011. e-Pub 12/2010. PMCID: PMC3007149.
7. 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 7/2006. PMCID: PMC1567685.
8. 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. PMCID: PMC525476.
9. Chao LY, Huff V, Tomlinson G, Riccardi VM, Strong LC, Saunders GF. Genetic mosaicism in normal tissues of Wilms' tumour patients. Nat Genet 3(2):127-31, 2/1993. PMID: 8388768.
10. Huff V, Compton DA, Chao LY, Strong LC, Geiser CF, Saunders GF. Lack of linkage of familial Wilms' tumour to chromosomal band 11p13. Nature 336(6197):377-8, 11/1988. PMID: 2848200.

Last updated: 2/18/2016