Investigator, Hale Family Research Center
Department Of Pathology, Brigham And Women’s Hospital & Dana-Farber Cancer Institute
Assistant Professor Of Pathology, Harvard Medical School
Dr. Jonathan Nowak, MD, PhD is a molecular and gastrointestinal pathologist at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, and assistant professor of pathology at Harvard Medical School. He specializes in the molecular characterization of solid tumors, with a specific focus on pancreatic and colorectal cancer, and runs a joint laboratory with Dr. Brian Wolpin focused on tissue-based analysis of human pancreatic cancer specimens.
Dr. Nowak earned his medical degree from the Weill Medical College of Cornell University and his doctorate of philosophy at The Rockefeller University as part of the Tri-Institutional Weill Cornell/Rockefeller/Sloan-Kettering MD-PhD Program. His graduate work in the laboratory of Dr. Elaine Fuchs identified the embryologic origin of skin epithelial stem cells and the transcriptional program necessary for their specification. He completed his pathology residency at Brigham and Women’s Hospital and fellowships at Harvard Medical School and Brigham and Women’s Hospital. He is board-certified in anatomic and clinical pathology and molecular genetic pathology. As a molecular pathologist, Dr. Nowak helps design and interpret next generation sequencing assays for clinical tumor characterization. He also leads a newly established constitutional genetics testing service focused on hereditary cancer predisposition. Dr. Nowak joined the faculty of Harvard Medical School, Brigham and Women’s Hospital, and the Dana-Farber Cancer Center in 2016.
The Wolpin-Nowak lab employs multiplexed immunofluorescence, digital image analysis and machine learning to study the microenvironment of pancreatic cancer using human tumor tissue specimens. The combination of these approaches allows us to study the components of the pancreatic cancer microenvironment at single cell resolution in their native, spatially-resolved configuration. This methodology provides rich, quantitative data that enable analyses not possible with traditional qualitative pathology approaches. We have developed assays to analyze both protein and RNA expression across a wide variety of cell types in pancreatic cancer. In particular, we have focused on immune cell infiltrates, tumor cell-specific markers indicative of different states of tumor differentiation, measuring cell cycle state, and analyzing stromal fibroblast composition.
A key advantage of our tissue-based assays is that they can be run at a large scale across hundreds of specimens. This allows us to generate uniform data sets across large cohorts of primary resected pancreatic cancer, neoadjuvant-treated pancreatic cancer and tissue specimens from patients who present with metastatic disease. The ability to customize targets of interest also makes our approach amenable to studying patient specimens collected from clinical trials and allows for biomarker discovery and validation using assays that can be implemented for routine clinical care.
As the key laboratory with pathology expertise in the Hale Family Research Center, we collaborate with other member laboratories to analyze the pathology of pancreatic cancer mouse models, patient-derived organoid and xenograft models, and to investigate the expression and morphologic correlates of specific pancreatic cancer biologic processes.
Liudahl SM, Betts CB, Sivagnanam S, Morales-Oyarvide V, da Silva A, Yuan C, Hwang S, Grossblatt-Wait A, Leis KR, Larson W, Lavoie MB, Robinson P, Dias Costa A, Vayrynen SA, Clancy TE, Rubinson DA, Link J, Keith D, Horton W, Tempero MA, Vonderheide RH, Jaffee EM, Sheppard B, Goecks J, Sears RC, Park BS, Mori M, Nowak JA, Wolpin BM, Coussens LM. Leukocyte Heterogeneity in Pancreatic Ductal Adenocarcinoma: Phenotypic and Spatial Features Associated with Clinical Outcome. Cancer Discov. 2021 Mar 16. PMID: 33727309.
Väyrynen SA, Zhang J, Yuan C, Väyrynen JP, Dias Costa A, Williams H, Morales-Oyarvide V, Lau MC, Rubinson DA, Dunne RF, Kozak MM, Wang W, Agostini-Vulaj D, Drage MG, Brais L, Reilly E, Rahma O, Clancy T, Wang J, Linehan DC, Aguirre AJ, Fuchs CS, Coussens LM, Chang DT, Koong AC, Hezel AF, Ogino S, Nowak JA, Wolpin BM. Composition, Spatial Characteristics, and Prognostic Significance of Myeloid Cell Infiltration in Pancreatic Cancer. Clin Cancer Res. 2021 Feb 15; 27(4):1069-1081. PMID: 33262135.
Väyrynen JP, Haruki K, Lau MC, Väyrynen SA, Zhong R, Dias Costa A, Borowsky J, Zhao M, Fujiyoshi K, Arima K, Twombly TS, Kishikawa J, Gu S, Aminmozaffari S, Shi S, Baba Y, Akimoto N, Ugai T, Da Silva A, Guerriero JL, Song M, Wu K, Chan AT, Nishihara R, Fuchs CS, Meyerhardt JA, Giannakis M, Ogino S, Nowak JA. The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment. Cancer Immunol Res. 2021 Jan; 9(1):8-19. PMID: 33023967.
Du C, da Silva A, Morales-Oyarvide V, Dias Costa A, Kozak MM, Dunne RF, Rubinson DA, Perez K, Masugi Y, Hamada T, Brais LK, Yuan C, Babic A, Ducar MD, Thorner AR, Aguirre A, Kulke MH, Ng K, Clancy TE, Findeis-Hosey JJ, Chang DT, Hornick JL, Fuchs CS, Ogino S, Koong AC, Hezel AF, Wolpin BM, Nowak JA. Insulin-Like Growth Factor-1 Receptor Expression and Disease Recurrence and Survival in Patients with Resected Pancreatic Ductal Adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2020 Aug; 29(8):1586-1595. PMID: 32467349.
Väyrynen JP, Lau MC, Haruki K, Väyrynen SA, Dias Costa A, Borowsky J, Zhao M, Fujiyoshi K, Arima K, Twombly TS, Kishikawa J, Gu S, Aminmozaffari S, Shi S, Baba Y, Akimoto N, Ugai T, Da Silva A, Song M, Wu K, Chan AT, Nishihara R, Fuchs CS, Meyerhardt JA, Giannakis M, Ogino S, Nowak JA. Prognostic Significance of Immune Cell Populations Identified by Machine Learning in Colorectal Cancer Using Routine Hematoxylin and Eosin-Stained Sections. Clin Cancer Res. 2020 08 15; 26(16):4326-4338. PMID: 32439699.
Yurgelun MB, Chittenden AB, Morales-Oyarvide V, Rubinson DA, Dunne RF, Kozak MM, Qian ZR, Welch MW, Brais LK, Da Silva A, Bui JL, Yuan C, Li T, Li W, Masuda A, Gu M, Bullock AJ, Chang DT, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Thorner AR, Ducar MD, Wollison BM, Khalaf N, Perez K, Syngal S, Aguirre AJ, Hahn WC, Meyerson ML, Fuchs CS, Ogino S, Hornick JL, Hezel AF, Koong AC, Nowak JA, Wolpin BM. Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. Genet Med. 2019 01; 21(1):213-223. PMID: 29961768.
Aguirre AJ, Nowak JA, Camarda ND, Moffitt RA, Ghazani AA, Hazar-Rethinam M, Raghavan S, Kim J, Brais LK, Ragon D, Welch MW, Reilly E, McCabe D, Marini L, Anderka K, Helvie K, Oliver N, Babic A, Da Silva A, Nadres B, Van Seventer EE, Shahzade HA, St Pierre JP, Burke KP, Clancy T, Cleary JM, Doyle LA, Jajoo K, McCleary NJ, Meyerhardt JA, Murphy JE, Ng K, Patel AK, Perez K, Rosenthal MH, Rubinson DA, Ryou M, Shapiro GI, Sicinska E, Silverman SG, Nagy RJ, Lanman RB, Knoerzer D, Welsch DJ, Yurgelun MB, Fuchs CS, Garraway LA, Getz G, Hornick JL, Johnson BE, Kulke MH, Mayer RJ, Miller JW, Shyn PB, Tuveson DA, Wagle N, Yeh JJ, Hahn WC, Corcoran RB, Carter SL, Wolpin BM. Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer Discov. 2018 09; 8(9):1096-1111. PMID: 29903880.
Qian ZR, Rubinson DA, Nowak JA, Morales-Oyarvide V, Dunne RF, Kozak MM, Welch MW, Brais LK, Da Silva A, Li T, Li W, Masuda A, Yang J, Shi Y, Gu M, Masugi Y, Bui J, Zellers CL, Yuan C, Babic A, Khalaf N, Aguirre A, Ng K, Miksad RA, Bullock AJ, Chang DT, Tseng JF, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Thorner AR, Ducar M, Wollison B, Laing A, Hahn WC, Meyerson M, Fuchs CS, Ogino S, Hornick JL, Hezel AF, Koong AC, Wolpin BM. Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2018 Mar 08; 4(3):e173420. PMID: 29098284.