Rivera Lab

Overview

Research in the Rivera laboratory focuses on using genomic tools to identify and characterize gene regulation pathways that are altered in cancer. An important feature shared by most tumors is the dysregulation of complex gene expression programs that control cell proliferation and differentiation. Our work combines the use of genomic technologies for the direct identification of gene regulation abnormalities in tumors with functional analysis of critical mechanisms and pathways. Given that the mechanisms that drive changes in gene expression programs in cancer are poorly understood, we anticipate that our studies will point to new therapeutic approaches.

Read more about the Rivera Lab from the Krantz Family Center for Cancer Research Annual Report.

Research Projects

Epigenomic approaches to identify critical pathways in cancer

We are using genomic technologies to identify abnormal gene regulation patterns in pediatric cancer. In particular, genome-wide chromatin profiling, which combines chromatin immunoprecipitation and high-throughput sequencing, is a powerful technology that can identify active and repressed states in the genome based on patterns of histone modifications. Our work using this technology has shown that Wilms tumors exhibit chromatin features typical of stem cells and that patterns of chromatin remodeling can reveal the mechanisms of action of aberrant transcriptional regulators such as the EWS-FLI1 fusion protein in Ewing sarcoma and the transcription factor OTX2 in medulloblastoma. We are now using a combination of biochemical and genomic tools to continue our analysis of these and other key transcriptional pathways in pediatric cancer.

Role of the WTX gene family in cancer and development

Wilms tumor, the most common pediatric kidney cancer, arises from kidney-specific stem cells and is a prime example of the connection between cancer and development. Through mapping genomic deletions in Wilms tumor we identified WTX, an X-linked tumor suppressor gene commonly inactivated in this disease and recently implicated in colon cancer. WTX is the founding member of a new protein family (FAM123) and our work using a conditional knockout mouse model has shown that it regulates mesenchymal stem cells in several organs, including kidneys, bones and fat. We are now studying the function of WTX and related proteins using several in vitro and in vivo model systems.

Group Members

Meet our research team:

• Miguel N. Rivera, MD
• Aliyu Alghali
• Rui Dong, PhD
• Miguel N. Rivera, MD
• Ian Roundtree, MD, PhD
• Karla Rubio, PhD
• Antonio Villanueva

Selected Publications

Xing YH, Dong R, Lee L, Rengarajan S, Riggi N, Boulay G, Rivera MN. DisP-seq reveals the genome-wide functional organization of DNA-associated disordered proteins. Nature Biotechnology. 2023 Apr 10.

Chebib I, Nielsen GP, Renella R, Cote GM, Choy E, Aryee M, Stegmaier K, Stamenkovic I, Rivera MN, Riggi N. Highly connected 3D chromatin networks established by an oncogenic fusion protein shape tumor cell identity. Science Advances. 2023 Mar 31.

Tak YE, Boulay G, Lee L, Iyer S, Perry NT, Schultz HT, Garcia SP, Broye L, Horng JE, Rengarajan S, Naigles B, Volorio A, Sander JD, Gong J, Riggi N, Joung JK, Rivera MN. Genome-wide functional perturbation of human microsatellite repeats using engineered zinc finger transcription factors. Cell Genomics. 2022 Apr 13.

Boulay G, Sandoval GJ, Riggi N, Iyer S, Buisson R, Naigles B, Awad ME, Rengarajan S, Volorio A, McBride MJ, Broye LC, Zou L, Stamenkovic I, Kadoch C, Rivera MN. Cancer-specific retargeting of BAF complexes by a prion-like domain. Cell. 171(1-16), 2017 Sept 21.

Riggi N, Knoechel B, Gillespie S, Rheinbay E, Boulay G, Suvà ML, Rossetti NE, Boonseng WE, Oksuz O, Cook EB, Formey A, Patel A, Gymrek M, Thapar V, Deshpande V, Ting DT, Hornicek FJ, Nielsen GP, Stamenkovic I, Aryee MJ, Bernstein BE, Rivera MN. EWS-FLI1 Utilizes Divergent Chromatin Remodeling Mechanisms to Directly Activate or Repress Enhancer Elements in Ewing Sarcoma. Cancer Cell. 26(5):668-81, 2014 Nov 10.

Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M, Kim JC, Feinberg AP, Gerald WL, Vargas SO, Chin L, Iafrate AJ, Bell DW, Haber DA. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science. 315(5812):642-5, 2007 Feb 2.