Matthew Benesch

December 2020

  • General Surgery PGY-3
  • Residency Program: Memorial University of Newfoundland
  • Supervisors: Dr. Alex Mathieson (Memorial University), Dr. Pagona Lagiou (Harvard University), Dr. David Brindley (University of Alberta), Dr. Todd McMullen (University of Alberta),

What research are you currently working on?
My most recent projects as part of my MPH include characterizing the epidemiology of signet ring cell and mucinous adenocarcinomas, as part of a larger project looking at optimal management of patients at risk of CDH1-mutation driven hereditary diffuse gastric cancers.  Prior to residency, my PhD work involved pre-clinical and clinical investigations into lipid-mediated signaling in cancer progression and therapy resistance.  I continue to contribute as an expert consultant in this field, with the first in-class inhibitor of relevant pathways currently in phase III clinical trials.

When did you become interested in Research?
I have been interested in research throughout my university career.  I conducted extensive research in my undergraduate in lipid biophysics, which wet my appetite and served as a stepping stone towards more clinically-applicable medical lipid-driven research in my MD/PhD.

How has research influenced your career goals?
I was drawn to finding clinical applications for my research. My projects had a natural application in cancer biology, and much of my initial PhD work involved using fresh specimens.  Consequently, I found myself increasingly interested in general surgery. I have used my research time in residency to round out my epidemiological skills. I hope to complete a fellowship in surgical oncology, and embark on a surgical career with a significant research component. As an independent investigator, I am interested in using epidemiology to guide patient selection for efficient biomarker design.

What is one piece of advice you would share to other residents interested in research?
Work on a project you are passionate about. If your heart is not into it, your progress will be suboptimal.  Similarly, if you identify a project you are invested in, start early – ethics, record procurement, collaborator input – these all take more time than you initially plan for.

What are the challenges of conducting research during residency?
General surgery is a hard lifestyle.  Work, research, personal time – often it feels you can only have two of these ever, at there will be times, including whole blocks, where work is the only thing you can do.  That is ok. The secret is planning things out early, and taking small bites of the project at a time.  Get fellow residents involved in the work – collaboration is the nature of the research business.  Review your project and concerns early and often with mentors and other appropriate support people to avoid costly mistakes.

What do you enjoy doing outside of residency/research?
Spending time with my fiancé. She is also in residency so navigating mutual time is difficult (we have a joint shared calendar for this).  Living in Newfoundland, there is no shortage of trials – we try to do these at least weekly.  Campfires are our favourite thing.

Any advice for approaching a potential research mentor?
Have some ideas in mind. Try and develop them a bit by reading a few relevant papers in the field.  Make it clear to the mentor what your outcome is – an abstract, poster, paper…advanced degree?  Use your peers and other academic advisors to also help you identify ideal mentors that you might consider working with.

Most memorable moment in research?
In my PhD I was struggling to develop a viable project, as most of my hypotheses did not work out and we could not figure out why.  Having a pilot drug experiment with mice go horribly wrong, I had to sacrifice these animals but I had a moment of inspiration that perhaps I was focusing my work on the wrong type of tissue.  It was a late Sunday night so I decided to do some PCR work on tissue I would normally discard.  In that tissue I found the mRNA levels I was long looking for.  I repeated that experiment twice that night to confirm my results.  In one evening, after 2.5 years of failed results, I suddenly had my entire PhD and several papers planned out by dawn.  Sometimes, research is about being at the right place at the right time, and always keeping a very open mind to alternative ideas.

Selected Publications

Benesch, M.G.K.; Bursey, S.R.; O’Connell, A.C.; Ryan, M.G.; Howard, C.L.; Stockley, C.C.; Mathieson, A. Outcomes of CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer: A Systematic Review of Endoscopic Surveillance and Population-Level Analysis Estimation of Secondary Cancer Risk. Ann. Surg Oncol. (Under Review).

Benesch, M.G.K.; Mathieson, A. Epidemiology of mucinous adenocarcinomas. Cancers (Basel) 2020, 12, 3193.

Benesch, M.G.K.; Mathieson, A. Epidemiology of signet ring cell adenocarcinomas. Cancers (Basel) 2020, 12, 1544.

Benesch, M.G.K.; Tang, X.; Brindley, D.N. Autotaxin and breast cancer: Towards overcoming treatment barriers and sequelae. Cancers (Basel) 2020, 12, 374.

Benesch, M.G.K.; MacIntyre, I.T.K.; McMullen, T.P.W.; Brindley, D.N. Coming of age for autotaxin and lysophosphatidate signaling: Clinical applications for preventing, detecting and targeting tumor-promoting inflammation. Cancers (Basel) 2018, 10, 73.

Benesch, M.G.K.; Yang, Z.; Tang, X.; Meng, G.; Brindley, D.N. Lysophosphatidate signaling: The tumor microenvironment’s new nemesis. Trends Cancer 2017, 3, 748-752.

Benesch, M.G.K.; Ko, Y.M.; Tang, X.; Dewald, J.; Lopez-Campistrous, A.; Zhao, Y.Y.; Lai, R.; Curtis, J.M.; Brindley, D.N.; McMullen, T.P. Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer. Endocr Relat Cancer 2015, 22, 593-607.

Benesch, M.G.K.; Tang, X.; Dewald, J.; Dong, W.F.; Mackey, J.R.; Hemmings, D.G.; McMullen, T.P.; Brindley, D.N. Tumor-induced inflammation in mammary adipose tissue stimulates a vicious cycle of autotaxin expression and breast cancer progression. FASEB J. 2015, 29, 3990-4000.

Benesch, M.G.K.; Tang, X.; Maeda, T.; Ohhata, A.; Zhao, Y.Y.; Kok, B.P.C.; Dewald, J.; Hitt, M.; Curtis, J.M.; McMullen, T.P.W., et al. Inhibition of autotaxin delays breast tumor growth and lung metastasis in mice. FASEB J. 2014, 28, 2655-2666.