Thakor Group

Opening for a postdoctoral fellow and a graduate student in the Thakor Lab

Thakor Research Group

Cellular and Molecular Medicine Lab

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

** Corresponding author

  1. 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
  2. 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. 
  3. 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.
  4. 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.
  5. 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. 
  6. 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.
  7. 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
  8. 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. 
  9. 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.
  10. 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. 
  11. 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. 
  12. 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.
  13. 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. 
  14. 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.

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 Associate Professor in the Department of Chemistry and Biochemistry 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 Department of Biological Sciences at U of L. 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 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

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.

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)

Brief Biography: I am a PhD student under the co-supervision of Dr. Nora Foroud (AAFC-Lethbridge) and Dr. Nehal Thakor (University of Lethbridge). I graduated from the University of Havana with a Bachelor's in Microbiology in 2007, and I completed my Master's in Microbiology in 2011. I arrived in Lethbridge in 2016 to start my Ph.D. in Biomolecular Sciences, and I am currently working at Agriculture and Agri-Food Canada (AAFC). My project involves the study of MAPK pathways in the phytopathogen Fusarium graminearum, and the role of these signaling cascades in plant-pathogen interaction.    

Veda Hegde

MSc Student: School of Graduate Studies Tuition and Dean’s Scholarship (2021-2022); 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).

Elizabeth Trofimenkoff

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

Brief Biography: I am currently an MSc student under the supervision of Dr. Marc Roussel and Dr. Nehal Thakor at the University of Lethbridge. I graduated with distinction from my undergraduate degree in Chemistry at the University of Lethbridge in 2020, where I was introduced to the wonderful world of mathematical modelling. This combined all of my interests into one discipline: math, chemistry and biochemistry. I am currently working with a number of mathematical models to identify eIF5B’s mechanistic role in a eukaryotic non-canonical translation initiation pathway involved in gliomagenesis, and possible ways to target this mechanism so a new therapy for those suffering from glioblastoma may be established.

Baillie Cej

BSc Student

Brief Biography: I am currently obtaining my bachelor of science degree at the University of Lethbridge. As part of the Thakor group, my summer project is focused on determining the optimal concentration of Temozolomide to administer brain tumor initiating cells (BTICs) by creating a kill curve for each BTIC lines used in the lab. My future project will involve delineating the role of eukaryotic initiation factor 5B (eIF5B) in carbon metabolism in BTIC cell lines. Hopefully, these data will help illustrate the fundamental role of eIF5B in cancer cell survival. 

Jason Luddu

BSc Student

I am an undergraduate 3rd year Biochemistry student who was recruited into the Thakor lab at the University of Lethbridge in the summer of 2022. Some of my hobbies include playing and refereeing soccer, running long distance races, and I also love growing plants all over my house. I am wanting to move forward into the area of pharmacy and/or pharmaceuticals after I finish my undergraduate degree. Although, working in the Thakor lab has widened my vision, and I would love to continue working in a research atmosphere for a couple more years at least. Right now I am learning the basics of the Thakor lab under the great guidance of Veda Hegde.

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.

    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: R&D Technologist at Sanofi Pasteur

    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

    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

    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​

    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.

    Postdoctoral Fellows:

    • Dr. Nilakshi Kulathunga (2021)

    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).

    BSc Students:

    • Carmen Agenbacht: Spring and Fall 2021
    • Kaden Ashcroft: Fall 2021
    • Amanda Reimer: Spring 2020.
    • Deesha Apparaju: AIHS Summer Studentship- 2019.
    • Kamiko Bressler: Chinook Summer Research Award (CSRA)-2016, NSERC-USRA-2017, Arts and Science Travel Award-2017. Completed Honours Thesis 2018.
    • Keiran Vanden Dungen: 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: CSRA-2017 and 2018.
    • Jessica Semmelrock: Summer 2017.
    • Keith Aubrey: NSERC-USRA-2018.
    • Olivia Marasco: CSRA-2018, CIHR undergraduate summer research award (2017) (co-supervised by Dr. Marc Roussel).
    • Anand Nambisan: MITACS-Globalink Award-2016.
    • Jesse Johnson: Spring 2016
    • Clay Kurtz: Spring 2016
    • Ethan Kutanzi: Spring 2016
    • Kaylie Graham: Spring 2016
    • Marisa Lelekach: Spring 2016, Summer 2016
    • Chris Cote: Fall 2015, Spring 2016
    • Rochelle Caruso: Fall 2015, Spring 2016
    • Ishani Moghe: Fall 2015, Spring 2016
    • Michelle Kwan: Summer 2015

    High School Students:

    • Pakeeza Mushtaq (High School Student; April 2018 to August 2018): Canada-Wide National Science Fair- Silver Excellence Medal.