Sarah Thayer, MD, PhD, FACS

Professor, Department of Surgery

Research

My research focus has been to investigate the genes that may contribute to the initiation, progression and regulation of cancer with a focus on breast and pancreatic cancer.

Pancreatic Stem Cell Compartment and PDAC

My early work focused on the role of a developmental gene, Shh, in pancreatic cancer (Nature 2003). This work revealed that Shh is upregulated early in pancreatic carcinogenesis and in response to chronic inflammatory injury. Although Shh plays an important later role in the biology of pancreatic cancer. This work led to the development of Shh inhibitors as a potential therapeutic target to treat cancer. This work led to ongoing work pancreatic into the cell of origin of pancreatic cancer published in PNAS, and Gastroenterology.

This work led to the identification of a novel pancreatic epithelial compartment, which we termed pancreatic duct glands (PDGs) (Gastroenterology 2010). This work shows that PDGs are mucinous compartment with a distinct molecular signature that expresses many that PDGs are a unipotent epithelial progenitor stem cell niche (Stem Cell Res 2015) and that PDGs may be the compartment of origin for pancreatic cancer (Gastroenterology 2016).

Circulating Tumor Cells and Cell Free DNA

The Thayer laboratory also works understanding and exploiting circulating tumor cells. The work with CTC has involved work to exploit CTC as a liquid biopsy to confirm diagnosis. In addition, the Thayer laboratory has investigated the importance of CTC as a prognostic marker and understanding these cells importance in the metastasis process. Genomic analysis of these cells identified as minimal residual disease has been used to identify mechanism of resistance and is being developed to guide additional therapies in breast cancer. The Thayer laboratory has developed molecular FISH based technologies to confirm CTC are of tumor origin. The ability to capture and genetically analyze true CTCs may be an extremely powerful tool not only to understand the biology of the primary tumor, migration, and metastasis, but also to ultimately identify novel chemotherapeutic targets for these cells (J Am Coll Surg 2015, Pancreas 2015, Small 2016, and Cancer Cytopathology 2017, SSO 2019, SABCS 2019).

Genomic Alteration and Cancer

My work with the ICGC and the PACGW focus on the genomic alterations in cancer. This work published in Nature, Nature Genetics and Nature communication has involved the analysis of genomic data to identify alterations that occur in cancer. These alterations provide insight into mechanism of cancer development and progression and may identify potential targets for therapeutic intervention.

Novel Target for Triple Negative Breast Cancer

My laboratory also focuses identifying and understanding novel target and biomarkers in breast cancer. One pathway being investigated by the Thayer laboratory is AMF. Autocrine Motility Factor (AMF), also known as Phosphoglucose Isomerase (PGI) or Neuroleukin (NLK), is a protein that has been implicated in poor prognosis in breast cancer. It is a multifunctional protein that can act both inside and outside of cells, and it has roles in several biological processes, such as glycolysis (a metabolic pathway that is often upregulated in cancer cells) and cell motility (the movement of cells). The AMF receptor is found on TNBC and is being investigated as a potential target for the treatment of the most lethal subtype of breast cancer.

Publications

Research Publications

Neha Zutshi, Bhopal Mahapartra, Pinaki Mondal, Wei An, Benjamin T Goetz, Shuo Wang, Sicong Li, Matthew D Storck, David Mercer, Adrian Black, Sarah P Thayer, Jennifer Black, Chi Lin, Vimla Band, Hamid Band. Cbl and Cbl-b Ubiquitin Ligases are Essential for Intestinal Epithelial Stem Cell Maintenance. BioRxiv 2023 May 23; doi: https://doi.org/10.1101/2023.05.17.541154
Akdemir, K.C., Le, V.T., Chandran, S. et al. Sarah Thayer (PCAWG Consortium) and Andrew Futreal. : Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer. Nat Genet (2023).
Yakneen, S., Waszak, S.M., PCAWG Technical Working Group. et al. Sarah Thayer (PCAWG Consortium): Butler enables rapid cloud-based analysis of thousands of human genomes. Nat Biotechnol 41, 577 (2023).
Marc Zapatka et al. Sarah Thayer (PCAWG Consortium) and Peter Lichter. The Landscape of viral associations in human cancers. Nature Genetics. 2023 21 March doi: https://doi.org/10.1038/s41588-019-0558-9
ICGC/TCGA Sarah Thayer (ICGC member) Pan-Cancer Analysis of whole genomes. Nature. 2023 614 E39
Isidro Cortes-Ciriano et al. Sarah Thayer (PCAWG Consortium) and Peter Park. Nature Genetics. 2023, 21 March
Li, Y., Roberts, N.D., Wala, J.A. et al. Sarah Thayer (PCAWG Consortium): Patterns of somatic structural variation in human cancer genomes. Nature 614, E38 (2023).
Rodriguez-Martin, B., Alvarez, E.G., Baez-Ortega, A. et al. Sarah Thayer (PCAGW Consortium): Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nat Genet (2023).
Rheinbay, E., Nielsen, M.M., Abascal, F. et al. Sarah Thayer (PCAGW Consortium): Analyses of non-coding somatic drivers in 2,658 cancer whole genomes. Nature 614, E40 (2023).
Yuan, Y., Ju, Y.S., Kim, Y. et al. Sarah Thayer (PCAGW Consortium): Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nat Genet (2023).
Gerstung, M., Jolly, C., Leshchiner, I. et al. Sarah Thayer (PCAWG Consortium) Author Correction: The evolutionary history of 2,658 cancers. Nature 614, E42 (2023).
PCAWG Transcriptome Core Group., Calabrese, C., Davidson, N.R. et al. Sarah Thayer (PCAWG Consortium): Genomic basis for RNA alterations in cancer. Nature 614, E37 (2023).
Ludmil Alexandrov, Jaegil kim et al. Sarah Thayer (PCAWG consortium) and Michael Stratton. The repertoire of Mutational signature in human Cancer. Nature 25 January 2023.
Carlevaro-Fita, J., Lanzós, A., Feuerbach, L. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis. Commun Biol 5, 1347 (2022).
Zhang, Y., Chen, F., Fonseca, N.A. et al. Sarah Thayer (PCAWG Consortium) Author Correction: High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations. Nat Commun 13, 7572 (2022).
Paczkowska, M., Barenboim, J., Sintupisut, N. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Integrative pathway enrichment analysis of multivariate omics data. Nat Commun 13, 7570 (2022).
Reyna, M.A., Haan, D., Paczkowska, M. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Pathway and network analysis of more than 2500 whole cancer genomes. Nat Commun 13, 7566 (2022).
Shuai, S., PCAWG Drivers and Functional Interpretation Working Group., Gallinger, S. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Combined burden and functional impact tests for cancer driver discovery using DriverPower. Nat Commun 13, 7571 (2022).
Sieverling, L., Hong, C., Koser, S.D. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Genomic footprints of activated telomere maintenance mechanisms in cancer. Nat Commun 13, 7574 (2022).
Cmero, M., Yuan, K., Ong, C.S. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Inferring structural variant cancer cell fraction. Nat Commun 13, 7568 (2022).
Jiao, W., Atwal, G., Polak, P. et al. Sarah Thayer (PCAWG Consotium) Author Correction: A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns. Nat Commun 13, 7573 (2022).
Rubanova, Y., Shi, R., Harrigan, C.F. et al. Sarah Thayer (PCAWG Consortium) Author Correction: Reconstructing evolutionary trajectories of mutation signature activities in cancer using TrackSig. Nat Commun 13, 7567 (2022).
Bhandari, V., Li, C.H., Bristow, R.G. et al. Sarah Thayer (PCAWG Consortium) and Boutros P (Author Correction: Divergent mutational processes distinguish hypoxic and normoxic tumours. Nat Commun 13, 7569 (2022).
Shi L, Suh W, Kavanaugh MM, Mills G, Thayer S, Shi R. Propensity Score Matching Analysis of the Effect of Payer Status on the Survival of Colon Cancer Patients. Cureus. 2021 Jun 18;13(6):e15748. doi: 10.7759/cureus.15748. PMID: 34285854; PMCID: PMC8286796.
Reames, Bradley N. MD, MS∗; Blair, Alex B. MD†; Krell, Robert W. MD‡; Groot, Vincent P. MD§; Gemenetzis, Georgios MD¶; Padussis, James C. MD∗; Thayer, Sarah P. MD, PhD∗; Falconi, Massimo MD||; Wolfgang, Christopher L. MD, PhD†; Weiss, Matthew J. MD∗∗; Are, Chandrakanth MD, MBA∗; He, Jin MD, PhD† Management of Locally Advanced Pancreatic Cancer, Annals of Surgery: June 2021 - Volume 273 - Issue 6 - p 1173-1181 doi: 10.1097/SLA.0000000000003568
Model of PDAC. In PANCREAS (Vol. 50, No. 7, pp. 1081-1081).
McAndrews, K.L., Maroni, D., Kansal, V., Mondal, P., Hollingsworth, M.A. and Thayer, S., 2021, August. Oncogenic Activation Within Tff2 Expressing Cells of the Pancreatic Ductal Glands Increase Stemness Prior to PDAC Formation in an Inducible Murine
Dirk Bausch, Stephan Fritz, Carlos Fernandez-del-Castillo, Andrew Warshaw, Sarah P. Thayer, and Andrew Liss. Hedgehog signaling promotes angiogenesis directly and indirectly in pancreatic cancer. Angiogenesis 2020 Aug;23(3): 479-492. PMID 32444947
Joo Kyung Park, Thomas Kank, Cally M Scherber, Keith Lillemoe, Carlos Fernandez, Andrew Warshaw Mehmet Toner, Daniel Irimia, Sarah P. Thayer Andrew Liss. Primary and Metastatic Pancreatic Cancer Cells Exhibit Differential Migratory Potentials. Pancreas, 2020 Jan; 49 (1): 128-134.
Xiang Liu, Dahn Clemens, James A Grunkemeyer, Jeffrey Price, Kelly O’Connell, Nora Chapman. Mucin-1 is required for Coxsake Virus B3-induced inflammation in Pancreatitis. Scientific Reports, 2019 Jul 23
11. Reames B, Blair AB, Krell RW, Groot VP, Gemenetzis G, Padussis J, Thayer SP, Falconi M, Wolfgang CL, Weiss MJ, Are C, and He J. Management of Locally Advanced Pancreatic Cancer-Results of an International Survey of Current Practice. Annals of Surgery,Aug 21, 2019. PMID 31449138
Magaret Tempero, Milenge Malafa, Gabriele Chiorean, Brian Czito, Courtney Scaife, Amol Narang, Chistos Fountzilas, Brian Wolpin, Mahmoud Al Hawary, Horacio Asbun, Stephen Behrman, Al BensonIII, Ellen Binder, Dana Cardin Chalres Cha, Vincent Chung, Mary Dillhoff, Efrat Dotan, Cristina Ferrone, George Fisher, Jeffrey Hardacre, William Hawkins, Andrew Ko, Noelle LoConte, Andrew Lowy, Cassadie Moravek, Eric Nakakura, Eileen O’Reilly, Jorge Obando, Sushanth Reddy, Sarah Thayer, Robert Wolff, Jennifer Burns and Grislda Zuccarino-Catania. NCCN Guidelines Insights: Pancreatic Adenocarcinoma Version 1.2019 Volume 17: issue 3 11 March 2019 Doi: https://doi.org/10.6004/jnccn.2019.0014
Rahat Jahan, Muzafar A. Macha, Ashu Shah, Sukhwinder Kaur, Sarah Thayer, Surinder K. Batra. Odyssey of trefoil factors in cancer. Journal of the National Cancer Institute (submitted, JCNI-19-1806)
Reames B; Blair B; Krell R; Padussis J; Thayer S; Falconi M; Wolfgang C; Weiss M; Are C; He J. Management of Locally Advanced Pancreatic Cancer: Results of an International Survey of Current Practice. Lancet Oncology (submitted) June 2019.11. Park JK; Hank T; Scherber CM; Lillemoe KD; Fernandez C; Warshaw AL; Toner M; Irima D; Thayer SP; Liss AS. Primary and metastatic pancreatic cancer cells exhibit differential magiratory potentials. Pancreas (Submitted) June 2019
onnor AA; Denroche RE; Jang GH; Lemire M; Zhang A; Chan-Seng-Yue M; Wilson G; Merico D; Lungu I; Bartlett JMS; Chadwick D; Liang S; Eagles J; Mbabaali F; Miller JK; Krzyzanowski P; Armstrong H; Luo Xuemei; Jorgensen LGT; Romero JM; Bavi P; Fischer S; Serra S; Bakhtiari SH; Caglar D; Roehrl MHA; Cleary S; Hollingsworth MA; Petersen G; Thayer S; Law CHL; Nanji S; Golan T; Smith AL; Borgida A; Dodd A; Hedley D; Wouters BG; O’Kane GM; Wilson JM; Zogopoulos G; Notta F; Knox JJ; Gallinger S. Integration of Genomic and Transcriptomic Features in Pancreatic Cancer Reveals Increased Cell Cycle Progression in Metastases. Cancer Cell, 11;35(2):267-282. February 11, 2019.
Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science (New York, N.Y.), 357(6356), 1156–1160.
Pergolino I; Morales-Oyarvide V; Mino-Kenudson M; Honselmann KC; Rosenbaum M; Nahar S; Kem M; Ferrone CR; Lillemoe KD; Bardeesy N; Ryan DP; Thayer SP; Warshaw AL; Fernandez-del Castillo C; Liss AS. Tumor engraftment in patient-derived xenografts of pancreatic ductal adenocarcinoma is associated with adverse clinicopathological features and poor survival. Accepted PLOS ONE.8Geller LT; Barzily-Rokni M; Danino T; Jonas OH; Shental N; Nejman D; Gavert N; Yaara Z; Cooper ZA; Shee K; Thaiss CA; Reuben A; Livny J; Avraham R; Frederick DT; Ligorio M; Chatman K; Johnston SE; Mosher CM; Brandis A; Fuks G; Gurbatri C; Vancheswaran G; Kim M; Hurd MW; Katz M; Fleming J; Maitra A; Smith DA; Skalak M; Bu J; Michaud M; Trauger SA; Barshack I; Golan T; Sandbank J; Flaherty KT; Mandinova A; Garrett WS; Thayer SP; Ferrone CR; Huttenhower C; Bhatia SN; Gevers D; Wargo JA; Golub TR; Straussman, R. (2017).
Geller LT; Barzily-Rokni M; Danino T; Jonas OH; Shental N; Nejman D; Cooper ZA; Shee K; Thaiss CA; Reuben A; Livny J; Avraham R; Frederick DT; Ligorio M; Chatman K; Johnston SE; Mosher CM; Smith DA; Skalak M; Bu J; Michaud M; Traugher SA; Flaherty KT; Mandinova A; Garrett WS; Thayer SP; Ferrone CR; Huttenhower C; Bhatia SN; Gevers D; Wargo JA; Golub TR; Straussman R. Intra-tumor bacteria elicit drug resistance in pancreatic ductal adenocarcinoma. Accepted Science 05/2017.
Connor AA; Denroche RE; Jang GH; Timms L; Kalimuthu SN; Selander I; McPherson T; Wilson GW; Chan-Seng-Yue MA; Borozan I; Ferretti V; Grant RC; Lungu IM; Costello E; Greenhalf W; Palmer D; Ghaneh P; Neoptolemos JP; Buchler M; Petersen G; Thayer SP; Hollingsworth MA; Sherker A; Durocher D; Dhani N; Hedley D; Serra S; Pollett A; Roehrl MH; et al. Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma. JAMA Oncology. 3 : 774-783. 2017.
Rosenbaum M; Cauley C; Kulemann B; Liss A; Fernandez C; Warshaw A; Lillemoe K; Thayer S; Pitman M. Cytologic Characteristics of Circulating Epithelioid Cells in Pancreatic Disease. Accepted Cancer Cytopathology, January 26, 2017.
Conner A, Denroche R, Jang GH, Timms L, Kalimuthu S, Selander I, McPherson T, Wilson G, Chan-Seng-Yue M, Borozan I, Ferretti V, Grant R, Lungu I, Costello-Goldring E, Greenhalf W, Palmer D, Ghaneh P, Neoptolemos J, Buchler M, Petersen G, Thayer S, Hollingsworth M, Sherker A, Durocher D, Dhani N, Hedley D, Serra S, Pollett A, Roehrl M, Bavi P, Bartlett J, Cleary S, Wilson J, Alexandrov L, Moore M, Wouters B, McPherson J, Notta Faiyaz, Stein L, Gallinger S. Distinct mutational signatures are associated with correlates of increased immune activity in pancreatic ductal adenocarcinoma. JAMA Oncology. 2016 Oct 20. doi: 10.1001/jamaoncol.2016.3916. [Epub ahead of print]
Saung MT, Sharei A, Adalsteinsson VA, Cho N, Kamath T, Ruiz C, Kirkpatrick J, Petal N, Mino-Kenudson M, Thayer SP, Langer R, Jensen KF, Liss AS, Love JC. A size-selective intracellular delivery platform. Small. 2016. Sep 4. doi: 10.1002/smll.201601155. [Epub ahead of print].
Yamaguchi J, Mino-Kenudson M, Liss AS, Chowdhury S, Wang, TC, Fernandez-del Castillo C, Lillemoe, KD, Warshaw AL, Thayer SP. Loss of trefoil factor 2 from pancreatic duct glands accelerates formation of intraductal papillary mucinous neoplasms. Gastroenterology. 2016. Dec;151(6):1232-1244.e10. doi: 10.1053/j.gastro.2016.07.045. PubMed PMID: 27523981. Epub 2016 Aug 12.

Education

Education & Training

Dr. Thayer earned an undergraduate degree in biology from Earlham College in Richmond, Indiana and a Master in Science degree in physiology and biology from Georgetown University in Washington, DC.

Her medical degree was awarded by the University of Virginia School of Medicine and her surgery residency was completed at Massachusetts General Hospital. Dr. Thayer continued her education earning a PhD at Cornell University Graduate School of Medical Sciences followed by a year of focused study in surgical oncology at Massachusetts General Hospital. Most recently, she completed coursework at the Harvard Business School focusing on Managing Health Care Delivery.

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