Present Title & Affiliation
Associate Professor, Department of Cancer Biology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX
The Schlacher lab research focuses on understanding molecular mechanisms of nuclear and mitochondrial DNA replication fork stability and their physiological outcomes, including how these processes suppress and direct tumorigenesis, disease and drug therapy responses. For this we use single molecule, single cell and in vivo approaches to focus on breast and ovarian cancer (BRCA) and Fanconi Anemia (FA) suppressor models, which is a prototypic cancer pre-dispositioning disease showing the broad spectrum of foundational hallmarks of cancer. We discovered the pathway of DNA replication fork protection involving the BRCA/FA disease suppressor genes, which are otherwise required for specialized repair of DNA damage. This Replication Fork Protection pathway has subsequently been confirmed to be intricately linked with Fanconi Anemia and BRCA/FA cancer suppression functions as well as to PARPi drug resistance mechanism in BRCA defective cells. Most recently, we discovered that FA and BRCA proteins are also required in the mitochondria for mitochondrial DNA replication stability, feasibly explaining many of the pleiotropic patient phenotypes important to cancer hallmarks that are linked to mitochondrial phenotypes. Importantly, we found that the mitochondrial DNA-dependent instability in FA/BRCA patient cells leads to a distinct cGAS/STAT1 inflammatory signaling that has been shown to promote proliferation and chemotherapy resistance, supporting physiologically distinct importance to this new yet unexplored mitochondrial genome stability pathway. We have developed unique Rad51c mouse models overcoming embryonic lethality by having created CRISPR/Cas9 edited hypomorphic Rad51c and polygenic Rad51c+Brca2 mutant mice, which develop cancer and Fanconi Anemia. The overall research plan of the Schlacher laboratory is to obtain an in-depth molecular and physiological understanding of DNA replication fork protection and stability in both the nucleus and the mitochondria. Our aspiration is that this new knowledge will provide the scientific framework for advanced biomarker development to eventually predict disease predisposition, drug treatment response and develop new treatment strategies including smart-design combination therapies.
Education & Training
|2006||University of Southern California, Los Angeles, CA, USA, PHD, Molecular Biology|
|2003||Karl-Franzens University, Graz, AUT, Magistra Rerum Naturales, Microbiology|
|2008-2013||Post-Doctoral Fellow, University of California, Department of Molecular and Medical Pharmacology, Los Angeles, CA|
|2007-2013||Post-Doctoral Fellow, Memorial Sloan-Kettering Cancer Center, Developmental Program, New York, NY|
Experience & Service
Senior Research Scientist, Division of Developmental Program, Memorial Sloan Kettering Cancer Center, New York, NY, 2013 - 2014
Senior Research Scientist, Department of Department for Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 2013 - 2014
Post-doctoral Fellow, Department of Department for Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 2008 - 2013
Post-doctoral Fellow, Department of Developmental Program, Memorial Sloan Kettering Cancer Center, New York, NY, 2007 - 2013
Fellow, Rita Allen Foundation, Houston, 2016 - Present
Fellow, Andrew Sabin Family Foundation, Houston, 2016 - 2017
Scholar in Cancer Biology, CPRIT, Houston, TX, 2014 - Present
Honors & Awards
|2016||Sabin Family Foundation Fellow, Andrew Sabin Family Foundation|
|2016||Rita Allen Foundation Scholar, Rita Allen Foundation|
|2014||CPRIT scholar in Cancer Biology, UT MD Anderson Cancer Center|
|2014||UT Rising STARs Award, UT STARs Program|
|2012||Nomination to Blavatnik Award, New York Academy of Sciences|
|2012||MSKCC Postdoctoral Research Award, Memorial Sloan-Kettering Cancer Center|
|2011||Parvin Foundation Award for academic excellence and lasting contributions to postdoctoral research in Biochemistry & Molecular Biology, University of California|
|2011||Molecular Biology Institute Research Excellence Award for outstanding postdoctoral research in Biochemistry & Molecular Biology, University of California|
|2011||Nomination to Chancellor’s Award for exceptional accomplishment in postdoctoral research, University of California|
|2011||EMS Best New Investigator Platform Presentation Award, selected from over 85 presentations by students and new investigators, Environmental Mutagen Society|
|2010||Award in recognition for best oral presentation by a postdoctoral fellow, Department of Molecular and Medical Pharmacology, University of California|
|2007||Berger Foundation Fellowship Award, Damon Runyon Cancer Research Foundation|
|2006||College Doctoral Research Prize in recognition for outstanding research by a Ph.D. student, College of Letters, Arts and Sciences, University of Southern California|
- Tomaszowski KH, Roy S, Guerrero C, Shukla P, Keshvani C, Chen Y, Ott M, Wu X, Zhang J, DiNardo CD, Schindler D, Schlacher K. Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress. Nat Commun 14(1):1333, 2023. e-Pub 2023. PMID: 36906610.
- Luzwick JW, Dombi E, Boisvert RA, Roy S, Park S, Kunnimalaiyaan S, Goffart S, Schindler D, Schlacher K. MRE11-dependent instability in mitochondrial DNA fork protection activates a cGAS immune signaling pathway. Sci Adv 7(51):eabf9441, 2021. e-Pub 2021. PMID: 34910513.
- Roy S, Luzwick JW, Schlacher K. SIRF: Quantitative in situ analysis of protein interactions at DNA replication forks. Journal of Cell Biology 217(4):1521-1536, 2018. e-Pub 2018. PMID: 29475976.
- Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell 145(4):529-42, 2011. PMID: 21565612.
- Longo, M., Roy, S., Chen, Y., Tomaszowski, K., Arvai, A.S., Pepper, J. T., Boisvert, R, A., Kunnimalaiyaan, S., Keshvani, C., Schild, D., Bacolla, A., Williams, G. J., Tainer J. A., and Schlacher. K. RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles. Nature Communications.