Fanconi Anemia; Hematology; Medical Oncology; Neoplasms by Histologic Type; Pediatrics; Therapeutics; Genomic Instability
Molecular Virology: Virology laboratories
Stem Cell Center, Yale: Stem Cell Self-Renewal and Cell Symmetry
The Kupfer lab works on the relationship of genomic instability and the propensity towards development of cancer. Specifically, we focus on the genetic syndrome Fanconi anemia (FA). Interestingly, children with FA are born with congenital anomalies and develop aplastic anemia and an assortment of leukemias and other cancers. Based on our interest on marrow failure and genomic instability, we have also started working on 3 related projects. First, we have begun to purify the protein complexes containing gene products that are defective in 2 additional hematopoietic failure syndromes, Diamond-Blackfan anemia (DBA) and congenital dyserythropoietic anemia (CDA). As in FA, the proteins (RPS19 for DBA, codanin for CDA) have no known function, and additional genes accounting for additional genetic complementation groups remain to be cloned and identified. Second, we are investigating ways to use our knowledge of genomic instability for improving cancer therapeutics. Finally, we have also started a more clinical project, using mass spectroscopy technology we have used to find FA binding proteins. Again in collaboration with the Semmes laboratory, we have adapted the mass spec to analyze sera from patients with pediatric malignancies in order to identify unique protein markers of disease. These markers could then be used for diagnosis, prognosis, staging, and tracking of minimum residual disease in patients. In addition, our goal is to identify interesting proteins for further analysis in our laboratory.
Specialized Terms: Genomic instability; Development of cancer; Genetic syndrome Fanconi anemia (FA); Viral protein enhancement of cancer therapeutics
Extensive Research Description
The Fanconi anemia core complex associates with chromatin during S phase.
Mi J, Kupfer GM. (2005). The Fanconi anemia core complex associates with chromatin during S phase. Blood 105(2):759-66.
Human T Cell Leukemia Virus I Tax1 Protein Sensitizes p53 Mutant Cells to DNA Damage.
Mihaylova V, Green A, Khurgel M, Semmes OJ, Kupfer GM. (2008) Human T Cell Leukemia Virus I Tax1 Protein Sensitizes p53 Mutant Cells to DNA Damage. Cancer Research, in press.
Full List of PubMed Publications
- Li J, Li W, Huang K, Zhang Y, Kupfer G, Zhao Q: Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward. J Hematol Oncol. 2018 Feb 13; 2018 Feb 13. PMID: 29433552
- Zhao W, Steinfeld JB, Liang F, Chen X, Maranon DG, Jian Ma C, Kwon Y, Rao T, Wang W, Sheng C, Song X, Deng Y, Jimenez-Sainz J, Lu L, Jensen RB, Xiong Y, Kupfer GM, Wiese C, Greene EC, Sung P: BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing. Nature. 2017 Oct 19; 2017 Oct 4. PMID: 28976962
- Brown PA, Shah B, Fathi A, Wieduwilt M, Advani A, Aoun P, Barta SK, Boyer MW, Bryan T, Burke PW, Cassaday R, Coccia PF, Coutre SE, Damon LE, DeAngelo DJ, Frankfurt O, Greer JP, Kantarjian HM, Klisovic RB, Kupfer G, Litzow M, Liu A, Mattison R, Park J, Rubnitz J, Saad A, Uy GL, Wang ES, Gregory KM, Ogba N: NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017. J Natl Compr Canc Netw. 2017 Sep. PMID: 28874594
- Liang F, Longerich S, Miller AS, Tang C, Buzovetsky O, Xiong Y, Maranon DG, Wiese C, Kupfer GM, Sung P: Promotion of RAD51-Mediated Homologous DNA Pairing by the RAD51AP1-UAF1 Complex. Cell Rep. 2016 Jun 7; 2016 May 26. PMID: 27239033
- Faustino EV, Li S, Silva CT, Pinto MG, Qin L, Tala JA, Rinder HM, Kupfer GM, Shapiro ED, Northeast Pediatric Critical Care Research Consortium.: Factor VIII May Predict Catheter-Related Thrombosis in Critically Ill Children: A Preliminary Study. Pediatr Crit Care Med. 2015 Jul. PMID: 25828784
- Longerich S, Li J, Xiong Y, Sung P, Kupfer GM: Stress and DNA repair biology of the Fanconi anemia pathway. Blood. 2014 Oct 30; 2014 Sep 18. PMID: 25237197
- Chen X, Wilson JB, McChesney P, Williams SA, Kwon Y, Longerich S, Marriott AS, Sung P, Jones NJ, Kupfer GM: The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization. J Biol Chem. 2014 Sep 12; 2014 Jul 28. PMID: 25070891
- Longerich S, Kwon Y, Tsai MS, Hlaing AS, Kupfer GM, Sung P: Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA. Nucleic Acids Res. 2014 May; 2014 Mar 12. PMID: 24623813
- Kupfer GM: Fanconi anemia: a signal transduction and DNA repair pathway. Yale J Biol Med. 2013 Dec 13; 2013 Dec 13. PMID: 24348213
- Chirnomas SD, Kupfer GM: The inherited bone marrow failure syndromes. Pediatr Clin North Am. 2013 Dec. PMID: 24237972
- Omer B, Kadan-Lottick NS, Roberts KB, Wang R, Demsky C, Kupfer GM, Cooper D, Seropian S, Ma X: Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults. Br J Haematol. 2012 Sep; 2012 Jul 6. PMID: 22775513
- Lo SM, Choi M, Liu J, Jain D, Boot RG, Kallemeijn WW, Aerts JM, Pashankar F, Kupfer GM, Mane S, Lifton RP, Mistry PK: Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis. Blood. 2012 May 17; 2012 Apr 4. PMID: 22493294
- Williams SA, Wilson JB, Clark AP, Mitson-Salazar A, Tomashevski A, Ananth S, Glazer PM, Semmes OJ, Bale AE, Jones NJ, Kupfer GM: Functional and physical interaction between the mismatch repair and FA-BRCA pathways. Hum Mol Genet. 2011 Nov 15; 2011 Aug 24. PMID: 21865299
- Williams SA, Longerich S, Sung P, Vaziri C, Kupfer GM: The E3 ubiquitin ligase RAD18 regulates ubiquitylation and chromatin loading of FANCD2 and FANCI. Blood. 2011 May 12; 2011 Feb 25. PMID: 21355096
- Halene S, Gao Y, Hahn K, Massaro S, Italiano JE Jr, Schulz V, Lin S, Kupfer GM, Krause DS: Serum response factor is an essential transcription factor in megakaryocytic maturation. Blood. 2010 Sep 16; 2010 Jun 4. PMID: 20525922
- Green AM, Kupfer GM: Fanconi anemia. Hematol Oncol Clin North Am. 2009 Apr. PMID: 19327579