Sam Workenhe

D.V.M., PhD

 sworkenh@uoguelph.ca
 Office: PAHL 4828
 519-824-4120 Ext. 54731

 Lab: PAHL 4814

 @samworkenhe

 

Profile

DVM, Addis Ababa University, Ethiopia

MSc, Marine Biotechnology, University of Tromso, Norway

PhD, Molecular Virology, University of Prince Edward Island, Canada

Postdoctoral Fellowship, Cancer Immunology & Immunotherapy, McMaster Immunology Research Center, Canada

Research Interests

Overview of Research Program

Our research program aims to understand how cell intrinsic processes such as sensing of pathogens, stress and metabolic states shape homeostatic processes such as activation of the immune system. To study these intricate processes, we use a variety of stimuli, including different classes of viruses, synthetic ligands and ligand-free genetic circuits in healthy and transformed cell lines established from evolutionarily divergent animal species. A common theme is to understand the crosstalk of distinct molecular processes that serve as an innate guard against invading pathogens and malignancies. We also study how these innate processes, such as the type I interferon system and programmed cell death, shape the development of adaptive immunity against viruses and cancer. We continue to translate the basic findings into novel therapeutics for cancer and viral diseases. 

Specific Projects

1. Decoding how viral associated ligands activate programmed cell death: Sensing of viral nucleic acids can activate a variety of antiviral responses, including programmed cell death. Mechanisms of nucleic acid sensing and activation of the interferon (IFN) response are widely studied. However, the role nucleic acid signaling proteins and downstream effectors, such as IFN-stimulated genes (ISGs), play in the activation of cell death remains largely unknown. Our laboratory uses synthetic circuits and a variety of genetic tools to study how antiviral signaling results in programmed cell death. The new findings of this study are crucial to manipulate programmed cell death in distinct pathophysiological states.

2. Pathophysiological outcomes of cell death: Programmed cell death is a highly regulated process with several immune-related organismal outcomes that can be pathogenic or therapeutic. We study in what instances can programmed cell death become pathogenic/therapeutic and what are the mediators of these immunological consequences. We utilize a variety of discovery tools such as Mass Spectrometry, Single Cell RNA Sequencing, and genome-scale CRISPR/Cas9 screening platforms to discover new immunobiology. The knowledge gained is required to develop novel immunotherapies for cancer and viral diseases.

3. Mechanisms of tumor detection by the immune system: The immune system is a powerful ally to eliminate malignant cells. Mechanisms by which immunotherapy refractory cancers, such as breast, pancreatic and brain tumors, evade anticancer immune responses remain largely unknown. We deploy a variety of immune-resistant tumor models and genetic tools to understand the biology of tumor-induced adaptive resistance mechanisms. Furthermore, our laboratory has the expertise to genetically engineer a variety of cancer-killing viruses that we often use as stimuli to understand changes in the tumor immune landscape. 

Funding agencies

Canadian Institute of Health Research

Ontario Institute of Cancer Research

Cancer Research Society

SickKids Foundation

OVC Pet Trust

BioCanRx

Livestock Research Innovation Corporation

We are accepting highly motivated students and postdoctoral fellows

We continue to welcome applications from talented and highly motivated graduate students and postdoctoral fellows. Please send me an email (sworkenh@uoguelph.ca) with your updated CV, transcripts and a statement of research interest outlining why you are interested to join our lab and how you will contribute to our research program.

Current Graduate Students

• Jordon Inkol, PhD Student
• Michael Westerveld, PhD Student, Former Undergraduate Honours Thesis Student
• Shayla Verburg, MSc student, Former BioCanRx Summer and Undergraduate Honours Thesis Student 
• Sarah Worfolk, MSc Student
• Leanne Feigelsohn, Undergraduate Summer Student

Former Graduate Students

Alumni

• Rebecca Lelievre, Summer USRA and 4th year Cellular and Molecular Biology thesis student
• Yi Lin Sun, 4th year Biomedical Sciences student and Volunteer  
• Ali Younis, MBS Student- 1 Year course based Masters degree
• Ghazal Mohseni, Mitacs Global Link Intern
• Lydia Bartels, Boehringer, Ingelheimer Veterinary Scholar 

Teaching

Principles of Disease in Veterinary Medicine - Instructor for Veterinary Virology (Unit 3) - 2022

Mechanisms of Disease - Invited Lecture on Cancer Immuntherapy - 2021, 2022

Cancer Biology - Invited Lecture on Tumor Immunology and Immunotherapy - 2022

Professional Experience & Honours

2022- SickKids New Investigator Award

2022 - Early Career Award - Livestock Research Innovation Corporation 

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

https://scholar.google.ca/citations?user=u40Ay9kAAAAJ&hl=en

https://pubmed.ncbi.nlm.nih.gov/?term=Workenhe+ST&size=50

Selected Publications

Viral-mediated activation and inhibition of programmed cell death. Verburg SG, Lelievre RM, Westerveld MJ, Inkol JM, Sun YL, Workenhe ST. PLoS Pathog. 2022 Aug 11;18(8):e1010718. doi: 10.1371/journal.ppat.1010718. 
 

LAMP3/CD63 Expression in Early and Late Endosomes in Human Vaginal Epithelial Cells Is Associated with Enhancement of HSV-2 Infection. Nazli A, Chow R, Zahoor MA, Workenhe ST, Dhawan T, Verschoor C, Kaushic C.J Virol. 2022 Nov 9:e0155322. doi: 10.1128/jvi.01553-22. Online ahead of print.

Cytokines in oncolytic virotherapy. Pol JG, Workenhe ST, Konda P, Gujar S, Kroemer G.Cytokine Growth Factor Rev. 2020 Dec;56:4-27. doi: 10.1016/j.cytogfr.2020.10.007.

Tumor-intrinsic determinants of immunogenic cell death modalities. Workenhe ST, Pol J, Kroemer G.Oncoimmunology. 2021 Mar 2;10(1):1893466. doi: 10.1080/2162402X.2021.1893466.

TRIM26 Facilitates HSV-2 Infection by Downregulating Antiviral Responses through the IRF3 Pathway. Dhawan T, Zahoor MA, Heryani N, Workenhe ST, Nazli A, Kaushic C.Viruses. 2021 Jan 6;13(1):70. doi: 10.3390/v13010070.

Immune checkpoint blockade in triple negative breast cancer influenced by B cells through myeloid-derived suppressor cells. Vito A, Salem O, El-Sayes N, MacFawn IP, Portillo AL, Milne K, Harrington D, Ashkar AA, Wan Y, Workenhe ST, Nelson BH, Bruno TC, Mossman KL.Commun Biol. 2021 Jul 12;4(1):859. doi: 10.1038/s42003-021-02375-9.

De novo necroptosis creates an inflammatory environment mediating tumor susceptibility to immune checkpoint inhibitors. Workenhe ST, Nguyen A, Bakhshinyan D, Wei J, Hare DN, MacNeill KL, Wan Y, Oberst A, Bramson JL, Nasir JA, Vito A, El-Sayes N, Singh SK, McArthur AG, Mossman KL. Commun Biol. 2020 Nov 4;3(1):645.

Search PubMed for additional publications by Dr. Workenhe.