• Office
  • PAHL 4828
  • 54731
  • Lab:
  • PAHL 4814

Samuel Workenhe

Assistant Professor   |   D.V.M., PhD

Profile

I am a trained Veterinarian and Molecular Virologist. I completed my Veterinary Medical training at Addis Ababa University, Ethiopia and subsequently joined graduate training in virology and immunology in Norway and Canada. My graduate training was focused on understanding the innate immunology of virus infections in Atlantic salmon.

During my postdoctoral training at McMaster University I developed a strong interest in understanding the fundamental aspects of programmed cell death and how it elicits immunity against viruses and growing tumors. We created several model systems to study programmed cell death and we continue to discover novel mechanisms of immune stimulation. Research in my lab will be instrumental in designing potent immunotherapies  for cancer and developing vaccines/ antivirals to control livestock diseases.

We opened my lab in September 2020, thus we are seeking to recruit highly motivated graduate students and postdoctoral fellows. If you are looking for a scientifically challenging environment to study the next frontiers of cell death and immunity research, please contact me directly or visit my lab’s website (workenhelab.ca).  

 

 

 

Research Interests

Programmed cell death and immunity in cancer: The ability of the immune system to recognize tumor cells as malignant entities is the foundation for the development of novel immunotherapies that have revolutionized cancer medicine. Certain types of cytotoxic anticancer therapies activate inflammatory cell death that facilitates immune-mediated recognition of tumors. The cytokines and danger molecules released during immunogenic cell death are vital for successful tumor-antigen presentation and adaptive immunity. In response to cytotoxic therapies tumors undergo programmed cell death that includes apoptosis, autophagy, pyroptosis and necroptosis. Most cytotoxic anticancer therapies have poor specificity for tumor cells and activate multiple types of programmed cell death. Moreover, different tumor types respond differently to cytotoxic therapies. As a result, it is difficult to identify relevant types of cell death that generate long-lasting antitumor immunity. The first goal of my lab’s research is to understand the host factors, immunological processes and tumor-intrinsic genetic factors that dictate immunotherapeutic outcome subsequent to activation of cell death.

 

Programmed cell death and immunity in virus infection: Viruses are ubiquitous genetic parasites in the biosphere, and virtually all organisms have evolved multiple defense mechanisms to cope with these parasites. At the heart of antiviral defenses are host-encoded receptors that can sense pathogen-associated molecular patterns to activate antiviral signaling cascade and programmed cell death, whereby an infected cell “commits altruistic suicide” to prevent spread of the virus to neighboring cells. Moreover, infected and dying cells can also secrete immuno-modulatory molecules that alarm the immune system. It is not known how different types of programmed cell death dictates antiviral immunity. The second goal of my lab’s research is to dissect mechanisms by which programmed cell death shapes adaptive antiviral immunity.

My lab's research is funded through OICR.

Professional Experience & Honours

2014 - Recipient of the Faculty of Health Sciences Outstanding Postdoctoral Achievement Award, McMaster University

2015 - Oncolytic Virus Conference Travel Award

2012 - American Society of Virology Travel Award

2008 - Recipient of Dr. Douglas W. Ehresmann Award, UPEI, Canada

2004 - 2006 - NORAD Graduate Student Fellowship, University of Tromso, Norway

Links

workenhelab.ca

Selected Publications

Workenhe ST*, et al., Mossman KL. Therapy induced Necroptosis renders non-immunogenic spontaneous tumors susceptible to checkpoint blockade immunotherapy. Accepted: Nature Communications Biology.

Pol JG, Lévesque S, Workenhe ST, Gujar S, Le Boeuf F, Clements DR, Fahrner J-E, Fend L, Bell JC, Mossman KL, Fucikova J, Spisek R, Zitvogel L, Kroemer G, Galluzzi L (2018). (2018). Trial Watch 2017 on Oncolytic viruses. Oncoimmunology, DOI: 10.1080/2162402X.2018.1503032.

Zakaria C, Sean P, Hoang HD, Leroux LP, Watson M, Workenhe ST, Hearnden J, Pearl D, Truong TV, Robichaud N, Yanagiya A, Tahmasebi S, Jafarnejad SM, Jia JJ, Graber TE, Fonseca BD, Pelin A, Diallo JS, Le Boeuf F, Bell JC, Mossman K, Jaramillo M, Sonenberg N, Alain T (2018). Active-Site mTOR Inhibitors Augment HSV1 Infection of Cancer Cells with Elevated eIF4E Activity. PLoS Pathog 14(8): e1007264.

Nguyen A, Ho L, Workenhe ST, Chen L, Samson J, Walsh SR, Pol J, Bramson JL, Wan Y. (2018). HDACi Delivery Reprograms Tumor-Infiltrating Myeloid Cells to Eliminate Antigen-Loss Variants. Cell Reports 24(3): 642-654.

Workenhe ST, van Vloten, JP, Wootton SK, Mossman KL, Bridle BW(2018). Critical interactions between immunogenic cancer cell death, oncolytic viruses and the immune system define the rational design of combination immunotherapies. Journal of Immunology. 200(2): 450-458.

Workenhe ST*, Ketela T, Moffat J, Mossman KL. Genome-wide lentiviral shRNA screen identifies Serine-arginine Rich Splicing Factor 2 as a determinant of oncolytic virus activity in breast cancer cells. Oncogene. 2016 May 12;35(19):2465-74.

Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, Bracci L, Breckpot K, Brough D, Buqu!e A, Castro MG, Cirone M, Colombo MI, Cremer I, Demaria S,  Dini L, Eliopoulos AG, Faggioni A, Formenti SC, Fucíkov J, Gabriele L, Gaipl US, Galon J, Garg A, Ghiringhelli F, Giese NA, Guo ZS, Hemminki A, Herrmann M, Hodge JW, Holdenrieder S, Honeychurch J, Hu HM, Huang X, Illidge TM, Kono K, Korbelik M, Krysko DV, Loi S, Lowenstein PR, Lugli E, Ma Y, Madeo F, Manfredi AA, Martins I, Mavilio D, Menger L, Merendino N, Michaud M, Mignot G, Mossman KL, Multhoff G, Oehler R, Palombo F, Panaretakis T, Pol J, Proietti E, Ricci JE, Riganti C, Rovere-Querini P, Rubartelli A, Sistigu A, Smyth MJ, Sonnemann J, Spisek R, Stagg J, Sukkurwala AQ, Tartour E, Thorburn A, Thorne SH, Vandenabeele P, Velotti F, Workenhe ST, Yang H, Zong WX, Zitvogel L, Kroemer G, and Galluzzi L (2014). Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology, 3:9, e955691.

Workenhe, ST, Verschoor, ML Mossman, KL (2015). The role of oncolytic virus immunotherapies to subvert cancer immune evasion. Future Oncology, 11(4) 675-689.

Workenhe, ST, Mossman KL (2014). Oncolytic virotherapy and immunogenic cancer cell death: sharpening the sword for improved cancer treatment strategies. Molecular Therapy, 22(2):251-6.

Workenhe, ST, Simmon, GJ, Pol JG, Lichty, BD, Halford WP, Mossman KL. HSV induced immunogenic oncolysis shapes the adaptive immune response and survival after oncolytic HSV-1 treatment. Molecular Therapy 2014, 22(1), 123–131.

Workenhe, ST, Mossman KL. Rewiring cancer cell death to enhance oncolytic viro-immunotherapy. Oncoimmunology 2013, 2:12, e27138.

Workenhe, ST, Pol JG, Lichty BD, Cummings DT, Mossman KL. Combining oncolytic HSV-1 with immunogenic cell death-inducing drug mitoxantrone breaks cancer immunotolerance and improves therapeutic efficacy. Cancer Immunology Research 2013, 1:1-11.