Thakor Group

Thakor Research Group

Cellular and Molecular Medicine Lab

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Research

In eukaryotic cells, the process of gene expression is tightly regulated at various levels including transcriptional, translational, and post-translational steps. Translational control is a critical component of the gene expression process that maintains cellular homeostasis during physiological and pathophysiological stress conditions. Moreover, the regulation of gene expression at the mRNA translation level allows cells to rapidly reprogram proteome output in response to stress stimuli. Dysregulation of protein synthesis has been implicated in various physiological disorders including cancer, Alzheimer's disease (AD), diabetes, stroke, X- linked Dyskeratosis Congenita (X-DC), etc. Extensive evidence exists suggesting that dysregulation of protein synthesis directs tumourigenesis by affecting both the global control of protein synthesis as well as the translation of specific subsets of transcripts. Accordingly, Thakor lab is investigating the cellular, biochemical, molecular, and structural aspects of the regulation of protein synthesis. We are interested in delineating the molecular mechanisms of both canonical, and non-canonical translation initiation and determining how these processes impact tumourigenesis.

Recent Publications:

Refereed:

* Trainee

§ equal contribution

** Corresponding author

  1. Hegde V*§, Sharma DK*§, Patel H*, Lakshmi PN*, Luddu J*, Holcik M, Thakor N** Eukaryotic initiation factor 3F (eIF3F) regulates the IRES-mediated translation of Bcl-xL via its interaction with programmed cell death 4 (PDCD4) protein. doi: https://doi.org/10.1101/2024.03.04.583409
  2. Shirokikh N**, Jensen KB, Reid JEA, Thakor N, Editorial: RNA Machines, Frontiers in Genetics. 2023, 2023 Sep 27; 14:1290420. https://doi.org/10.3389/fgene.2023.1290420
  3. Tiwari S*, Shahat A, Kastelic J, Thakor N**, Thundathil J** Optimized total RNA isolation from bovine sperm with enhanced sperm head lysis. (2023 Nov 10. https://doi.org/10.1139/bcb-2023-0231 Biochemistry and Cell Biology, 2024, 102(2), 194 (Invited- Special Collection RiboWest2023)
  4. Shostak K*, § Gonzalez-Pena DF*, § Witte T, Blackman C, Sproule A, Overy D, Eranthodi A, Thakor N, Foroud N**, Subramaniam R** Epistatic relationship between MGV1 and TRI6 in the regulation of biosynthetic gene clusters in Fusarium graminearum. Journal of Fungi. 2023, 9(8), 816; https://doi.org/10.3390/jof9080816
  5. Chukka P*, Wetmore S**, Thakor N** Established and Emerging Regulatory Roles of Eukaryotic Translation Initiation Factor 5B (eIF5B). Frontiers in Genetics (Invited- Special Issue on RNA Machines) (Review). Accepted Aug 2021. Doi: 10.3389/fgene.2021.737433
  6. Marasco ONJM*, Marc R. Roussel**, Thakor N Probabilistic models of uORF-mediated ATF4 translation control. Mathematical Biosciences (Invited- Special theme on Dynamic Publication Media in Mathematical Biology). 2022, 343, 108762 DOI: 10.1016/j.mbs.2021.108762.
  7. Bressler KR*§, Ross JA*§, Ilnytskyy S*§, Vanden Dungen K*, Taylor K*, Patel K*, Zovoilis A, Kovalchuk I, Thakor N** (§ Contributed equally; co-first authors) Depletion of eukaryotic initiation factor 5B (eIF5B) reprograms the cellular transcriptome and leads to activation of endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK). Cell Stress and Chaperones. 2021, 26(1), 253 DOI: 10.1007/s12192-020-01174-1.
  8. Cheng Y*, Saville L*, Gollen B*, Isaac C*, Mehla J*, Patel K*, Thakor N, Mohajerani M, Zovoilis A** Increased processing of SINE B2 non-coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology. eLife. 9;e61265; doi: 10.7554/eLife.61265.
  9. Balasingam N*, Brandon H*, Ross J*, Wieden HJ**, Thakor N** Cellular roles of human Obg-like ATPase 1 (hOLA1) and its bacterial homologue, YchF. Biochemistry and Cell Biology (Invited- Special Issue RiboWest2018) (Review); 2020, 98(1), 1-11; doi: 10.1139/bcb-2018-0353.
  10. Thakor N, Kothe U, Wieden HJ, Patel T. Proceedings of the 14th annual RiboWest conference: perspectives and outcome. Biochemistry and Cell Biology. 2020, 98(1). Vii-ix. doi: 10.1139/bcb-2019-0187.
  11. Foroud NA**, Baines D, Gagkaeva TY, Thakor N, Badea A, Steiner B, Bürstmayr M, Bürstmayr H. Trichothecenes in Cereal Grains- an Update. Toxins (Review) 2019, 11(11), 634; doi: 10.3390/toxins11110634
  12. Ross JA*, Ahn BA*, King J*, Bressler KR*, Senger DL, Thakor N** Eukaryotic initiation factor 5B (eIF5B) regulates temozolomide-mediated apoptosis in brain tumor stem cells (BTSCs). Biochemistry and Cell Biology (Invited- Special Issue Alberta Epigenetic Network Summit-2019). 2020, 98(6), 647 DOI: 10.1139/bcb-2019-0329.
  13. Nshogozabahizi JC*, Aubrey KL*, Ross J**, Thakor N** Applications and limitations of RNA elements in synthetic biology and biotechnology. Journal of Applied Microbiology (Review) 2019, 127(4), 968-984; doi: 10.1111/jam.14270.
  14. Ross J*, Vanden Dungen K*, Bressler K*, Fredriksen M*, Sharma D*, Balasingam N* and Thakor N** Eukaryotic initiation factor 5B (eIF5B) provides a critical cell survival switch to glioblastoma cells via regulation of apoptosis. Cell Death and Disease 2019, 10(2), 57 doi: 10.1038/s41419-018-1283-5.
  15. Ross J*§, Bressler K*§, and Thakor N** (§ Contributed equally; co-first authors). Eukaryotic Initiation Factor 5B (eIF5B) Cooperates with eIF1A and eIF5 to Facilitate uORF2-Mediated Repression of ATF4 Translation. International Journal of Molecular Sciences (Special issue- Translational Control) 2018, 19(12), 4032; doi:10.3390/ijms19124032.
  16. Ross, J.A.* and Thakor, N** Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs. Journal of Visual Experimentation (JoVe) (Invited), 2018, 10(135): 57519, :10.3791/57519.
  17. Thakor, N.**, Smith, M. D., Roberts, L.*, Faye, M. D.*, Patel, H.*, Wieden H. J., Cate, J. H. D., Holcik, M.** Cellular mRNA recruits the ribosome via eIF3-PABP bridge to initiate internal translation. RNA Biology, 2017, 14(5): 553-567.
  18. Sharma D*§, Bressler K*§, Patel H*§, Balasingam N*, and Thakor N.**; (§ Contributed equally; co-first authors). Role of eukaryotic initiation factors (eIFs) during cellular stress and cancer progression. Journal of Nucleic Acids (Invited Review Article), 2016, 8235121 http://dx.doi.org/10.1155/2016/8235121; PMID: 28083147.

Theses:

PhD
MSc

Current Lab Members

Dr. Nehal Thakor

Brief Biography: I was recruited to the University of Lethbridge as an Assistant Professor and Campus Alberta Innovates Program Research Chair in 2014. Currently, I am a tenured Full Professor in the Department of Biological Sciences at U of L. I am also affiliated with the Arnie Charbonneau Cancer Institute (Cumming School of Medicine, University of Calgary), the Southern Alberta Genome Sciences Centre (SAGSC) as well as the Canadian Centre for Behavioural Neuroscience at U of L. I am an active member of RNA Canada ARN and my laboratory is an integral part of the RNA Innovation program. I have a long-standing interest in studying the regulation of mRNA translation (protein synthesis) in both bacteria and eukaryotic cells. My current research is focused on understanding mechanisms of non-canonical translation initiation during cellular stress and oncogenesis. To this end, my laboratory employs various cell biology, molecular biology, biochemistry, and genomics techniques. Our research is/has been funded by highly competitive grants from various funding agencies such as American Brain Tumour Association, Cancer Research Society, Natural Sciences and Engineering Research Council of Canada, New Frontiers in Research Fund, Campus Alberta Innovates Program (Government of Alberta), Alberta Innovates, and Rare Disease Foundation of Canada.

E.mail: nthakor@uleth.ca; Phone: 403-317-5055

Dr. Tithi Ghosh

Postdoctoral Fellow

Brief Biography: I recently completed my doctoral studies in cellular and molecular biology at the Université de Sherbrooke, QC, Canada, supported by an NSERC-funded CREATE fellowship. During my PhD, I focused on molecular microbiology, investigating protein binding sites on bacterial riboswitches in E. coli. Now, as a postdoctoral researcher in Dr. Thakor's lab, I have transitioned into cancer biology. My current research project focuses on studying the regulation of mRNA translation in glioblastoma and oral squamous cell carcinoma. In addition to my academic pursuits, I have gained valuable industrial experience through positions at the Canadian Nuclear Laboratory, Corteva Agriscience, and Tatum Bioscience. I have also contributed to scientific discourse by publishing articles from my PhD studies and served as an editorial mentor for a high school journal. All these experiences have reinforced my commitment to advancing knowledge and nurturing the next generation of scientists.

Pavan Lakshmi Narasimha

PhD Student: School of Graduate Studies Tuition Award (2021-2024); Alberta Innovates Graduate Fellowship (2021-2024) (co-supervised by Dr. Mehdi Jafarnejad)

Brief Biography: I obtained my master’s degree from the University of Nottingham (UK). During my master’s program, I worked in the area of translational breast cancer biology. I joined the PhD program in the Thakor lab in 2021. I study the mechanistic aspects of mRNA translation that impact survival, proliferation, invasion and migration of glioblastoma. For my studies, I use preclinical models such as patient-derived brain tumor stem cells (BTSCs) and orthotopic xenograft mouse models. My preclinical work in the Thakor lab has the potential to provide mechanistic insight into GBM biology and ultimately improve patient outcomes.

Saurabh Tiwari

PhD Student: (2021-2025) (Co-supervised by Dr. Jacob Thundathil; Faculty of Veterinary Medicine, University of Calgary)

Brief Biography: I am a graduate (PhD) student at University of Calgary, Canada, with a research background in reproductive physiology. I will conduct my doctoral research in collaboration with University of Lethbridge under co-supervision of Dr. Nehal Thakor. My research focus is to augment fertility in farm animals and address infertility in several species with an improved understanding of gamete biology.

Veda Hegde

PhD Student: School of Graduate Studies Tuition and Dean’s Scholarship (2021-2024); Alberta Innovates Graduate Fellowship (2021-2022)

Brief Biography: Currently, I am a first-year master's student at the Thakor Lab. I come from a background in tumor immunology and obtained my MSD at the University of Essex, UK. During my research program, I investigated the role of zinc finger proteins in the immune pathways of tumor cells. I am now studying the role of a tumor suppressor protein PDCD4 in non-canonical translation initiation. My ongoing work in the Thakor lab has the potential to delineate the molecular mechanisms of mRNA translation initiation during stress and cancer.

Jinay Patel

MSc Student: School of Graduate Studies Tuition Award (2021-2023), NSERC-CREATE

Brief Biography: I am an MSc student in the Thakor lab. I completed my undergraduate degree at the University of Lethbridge where I majored in biochemistry. An undergraduate honours thesis project in the Thakor lab got me excited about cancer biology and my current project is focused on translation initiation and it’s role in the survival of oral squamous cell carcinoma (OSCC).

Priyanshi Patel

BSc Student

Brief Biography: I am an undergraduate student at the University of Lethbridge majoring in Biochemistry. I became a part of the Thakor lab in the summer of 2023. Outside of the lab, I enjoy playing volleyball, hiking, and spending time with my friends and family. Currently, I have gotten the opportunity to learn the basics of biochemistry and cancer biology. Working in the Thakor lab has allowed me to discover my passion for working in a research environment. I hope to work in this research environment for a couple of years before pursuing a career in the medical field.

Hannah Stephenson

BSc Student

Brief Biography: I am an undergraduate 3rd year Biochemistry student who was recruited into the Thakor lab at the University of Lethbridge in the summer of 2023. I am currently working and learning the basic biochemistry and cell biology techniques. I hope to continue working in this research environment for the next couple of years. After my undergraduate degree, I hope to pursue a profession in the medical field.

Former Lab Members:

Dr. Joseph A. Ross

Postdoctoral Fellow (2016-2019)

RNA society travel award for RiboClub2018, NSERC-CREATE., CCSRI Travel Award 2019.

Current Position: Senior Scientist at the Chinook Contract Research.

Dianevys Gonzalez-Pena Fundora

PhD Student: School of Graduate Studies International Tuition (2016-2020), School of Graduate Studies Fellowship (2016), AITF Graduate Fellowship (2017-2019), Coca-Cola Award (2016) Canadian Phytopathological Society Graduate Student Scholarship (2018) (co-supervised by Dr. Nora Foroud)

Current Position: Postdoctoral Fellow, Lethbridge Agriculture Research Centre

Divya Sharma

MSc Student: School of Graduate Studies Tuition (2015-2017), and Travel Awards (2017); Dean’s Scholarship (2015-2017); First Prize poster presentation in MSc category in Chinook Symposium of Chemistry and Biochemistry-2016; RNA society travel award for RiboClub2017.

Current position: Lead Research Engineer at Siemens Healthineers

Nirujah Balasingam

MSc Student: School of Graduate Studies Tuition (2015-2017), and Travel Awards (2017).

Current Position: Research Associate II, Providence Therapeutics

Prakash Chukka

MSc Student: School of Graduate Studies Tuition Award (2019-2022), NSERC-CREATE, (co-supervised by Dr. Stacey Wetmore).

Current Position: Associate Scientist I at Molecular Forecaster

Kamiko Bressler

MSc Student: School of Graduate Studies Tuition and Dean’s Scholarship (2018-2019); Queen Elizabeth 2 Graduate Scholarship (2018); NSERC-CGS (2018-2019).

Current Position: MD Candidate at the University of Calgary

Elizabeth Trofimenkoff

MSc Student: School of Graduate Studies Tuition Award (2020-2022) (co-supervised by Dr. Marc Roussel)

Current Position: PhD Student (Roussel Lab)

Razia Sultana

MSc Student (Co-supervised by Dr. Trevor Alexander)

Dr. Harshil Patel

BSc Student: CSRA-2015, NSERC-USRA-2016.

Current Position: Medical Doctor

Resident Physician - Internal Medicine

Cumming School of Medicine

University of Calgary​

Kush Patel

BSc Honours Student: NSERC-USRA-2019, 2020, 2021; NSERC-CREATE- 2020 and 2021.

Current Position: MD Candidate at the University of Calgary

Katrina Taylor

BSc Honours Student: NSERC-USRA-2020, Alberta Innovates 2021.

Current Position: MD Candidate at the University of Calgary

Mikayla Fredriksen

BSc Student: Fall 2016, Spring 2017, Fall 2017, and Spring 2018.

Current Position: MD Candidate at the University of Alberta

Brianna-Marie Lee

BSc Student: Spring and Fall 2019.

Current Position: Master of Health Services Management program at UofL Calgary campus.

Baillie Cej

BSc Student

Current Position: Graduate Student, University of Heidelberg

Postdoctoral Fellows:

  • Dr. Nilakshi Kulathunga (2021)
  • Dr. Himanshu Mali (2023)

MSc Students:

  • Keith Aubrey (M.Sc. Student): School of Graduate Studies Tuition Award (2018-2020), NSERC-CREATE.
  • Rachana Muley (M.Sc. Student): School of Graduate Studies Tuition Award (2017-2020).
  • Keiran Vanden Dungen (M.Sc. Student): School of Graduate Studies Tuition and Queen Elizabeth 2 Graduate Scholarship (2018); AITF Graduate Fellowship (2018-2020).

Honours Thesis Students:

  • Jason Luddu: Fall 2023-Spring 2024
  • Jinay Patel: Fall 2020- Spring 2021
  • Kamiko Bressler: Fall 2017- Spring 2018
  • Katrina Taylor: Fall 2020- Spring 2021
  • Keiran Vanden Dungen: Summer 2017- Fall 2017
  • Kush Patel (Co-supervised by Dr. Gerlinde Metz): Fall 2021- Spring 2022
  • Leeann Klassen (Co-supervised by Dr. Wade Abbott): Spring 2016- Summer 201

BSc Students (Independent Study):

  • Aria Carpentier: Fall 2023, Spring 2024
  • Abeer Abdullah: Summer 2016 (Graduate Student from Dr. Ute Kothe lab)
  • Amanda Reimer: Spring 2020.
  • Baillie Cej: Summer 2022, Fall 2022
  • Brianna-Marie Lee: Spring 2019, Fall 2019
  • Carmen Agenbacht: Spring and Fall 2021
  • Chris Cote: Fall 2015, Spring 2016
  • Clay Kurtz: Spring 2016
  • Deesha Apparaju: Spring 2019 and Fall 2019.
  • Ethan Kutanzi: Spring 2016
  • Harshil Patel: Fall 2015
  • Hunter Johnson: Spring 2020 (Research Internship Concentration Student; Biology)
  • Ishani Moghe: Fall 2015, Spring 2016
  • Jason Luddu: Summer 2022, Fall 2022, Spring 2023
  • Jesse Johnson: Spring 2016
  • Jessica Semmelrock: Summer 2017.
  • Justin Olsen: Spring 2018.
  • Kaden Ashcroft: Fall 2021
  • Kamiko Bressler: Spring 2016, Fall 2016, Spring 2017.
  • Katrina Taylor: Spring 2020 (Research Internship Concentration Student; Biology),
  • Kaylie Graham: Spring 2016
  • Keiran Vanden Dungen: Spring 2017, Fall 2017, Spring 2018.
  • Keith Aubrey: Spring 2017 (Experiential Learning student from the Quest University), Fall 2017.
  • Kush Patel: Spring 2019, Spring 2020, Fall 2020, Spring 2021
  • Marisa Lelekach: Spring 2016, Summer 2016
  • Mikayla Fredriksen: Fall 2016, Spring 2017, Fall 2017, Spring 2018 (Emergency Medicine Resident, Alberta Health Services)
  • Nicolas Parra: Spring 2023, Summer 2023; Fall 2023
  • Olivia Marasco: Fall 2017.
  • Rochelle Caruso: Fall 2015, Spring 2016

High School Students:

  • Pakeeza Mushtaq (High School Student; April 2018 to August 2018): Canada-Wide National Science Fair- Silver Excellence Medal.
  • Scarlett Davis (2023), Highschool Youth Researcher Summer (HYRS) Program

Trainee Awards:

Postdoctoral Fellows

  • Dr. Joseph A. Ross (Postdoctoral Fellow; 2016-2019): RNA society travel award for RiboClub2018, NSERC-CREATE, CCSRI Travel Award 2019 (declined)

PhD Students

  • Fundora (Ph.D. Student): School of Graduate Studies Tuition (2015-2019), School of Graduate Studies Graduate Fellowship (2016); First prize poster presentation in 88th Annual Meeting of the Canadian Phytopathological Society, AITF Graduate Fellowship 2018-2019, Canadian Phytopathological Society Graduate Student Scholarship (co-supervised by Dr. Nora Foroud).
  • Veda Hegde (Ph.D. Student: transferred to Ph.D. Program in my lab effective from Jan 2023): University of Lethbridge Graduate Research Award; Alberta Innovates Graduate Fellowship (2021-2024; with transfer to PhD program)
  • Pavan Lakshmi Narasimha (Ph.D. Student): School of Graduate Studies Tuition Award (2021-2024); Alberta Innovates Graduate Fellowship (2021-2024)
  • Saurabh Tiwari (Ph.D. Student): Second Prize for Oral Presentation at the RiboWest2023 conference; Alberta Graduate Excellence Scholarship (15,000 CAD) (2021-2022); Graduate teaching assistant (September-December 2022), VETM-601 (Professional Skills in Health Sciences Research); Graduate non-teaching assistant (July-August 2022); Professional Skills Development Award (1000 CAD) (2022).

MSc Students

  • Jinay Patel (M.Sc. Student): School of Graduate Studies Tuition Award (2021-2023), NSERC-CREATE.
  • Veda Hegde (M.Sc. Student): School of Graduate Studies Tuition and Dean’s Scholarship (2021-2022); Alberta Innovates Graduate Fellowship (2021-2022); WinSTEM scholar award for best female presenter during Chinook Symposium of Chemistry and Biochemistry (2022)
  • Elizabeth Trofimenkoff (M.Sc. Student): School of Graduate Studies Tuition Award (2020-2022) (co-supervised by Dr. Marc Roussel).
  • Prakash Chukka (M.Sc. Student): School of Graduate Studies Tuition Award (2019-2021), NSERC-CREATE.
  • Keith Aubrey (M.Sc. Student): School of Graduate Studies Tuition Award (2019-2020), NSERC-CREATE.
  • Rachana Muley (M.Sc. Student): School of Graduate Studies Tuition Award (2017-2020).
  • Kamiko Bressler (M.Sc. Student): School of Graduate Studies Tuition and Dean’s Scholarship (2018-2019); Queen Elizabeth 2 Graduate Scholarship (2018); NSERC-CGS (2018-2019).
  • Keiran Vanden Dungen (M.Sc. Student): School of Graduate Studies Tuition and Queen Elizabeth 2 Graduate Scholarship (2018); AITF Graduate Fellowship (2018-2020)
  • Balasingam (M.Sc. Student): School of Graduate Studies Tuition (2015-2017), and SGS Travel Award for RiboWest20217.
  • Divya Sharma (M.Sc. Student): School of Graduate Studies Tuition (2015-2017), and Travel Awards (2017); Dean’s Scholarship (2015-2017); RNA society travel award for RiboClub2017; First Prize poster presentation in MSc category in Chinook Symposium of Chemistry and Biochemistry-2016; SGS Travel Award for RiboWest2017.

BSc Students

  • Kamiko Bressler (B.Sc. Student): Chinook Summer Research Award (CSRA)-2016, NSERC-USRA-2017, Arts and Science Travel Award-2017; First Prize poster presentation in BSc category in Chinook Symposium of Chemistry and Biochemistry-2016. Completed Honours Thesis 2018.
  • Keiran Vanden Dungen (B.Sc. Student): NSERC-USRA 2018, First Prize Poster presentation in BSc category in RiboWest2017 (2017); Second Prize poster presentation in BSc category in Chinook Symposium (2017). Completed Honours Thesis 2017.
  • Justin Olsen (B.Sc. Student): CSRA-2017 and 2018.
  • Olivia Marasco (B.Sc. Student): CSRA-2018, CIHR undergraduate summer research award (2017) (co-supervised by Dr. Marc Roussel).
  • Harshil Patel (B.Sc. Student): CSRA-2015, NSERC-USRA-2016.
  • Anand Nambisan (B.Sc. Student): MITACS-Globalink Award-2016.
  • Keith Aubrey (B.Sc. Student): NSERC-USRA-2018.
  • Deesha Apparaju (B.Sc. Student): AIHS Summer Studentship- 2019.
  • Kush Patel (B.Sc. Student): NSERC-USRA-2019, 2020, 2021; NSERC-CREATE- 2020 and 2021
  • Katrina Taylor (B.Sc. Student): NSERC-USRA-2020, Alberta Innovates 2021.
  • Jason Luddu (B.Sc. Student): CSRA-2023, Exceptional Oral Presentation Award in RiboWest2023.
  • Priyanshi Patel (B.Sc. Student): Alberta Innovates Summer Studentship- 2023, NSERC-USRA-2024
  • Ryley Chalack (B.Sc. Student): NSERC-USRA-2024

American Brain Tumour Association