捆绑SM社区

Dr. Ivan Litvinov

Academic title(s): 

Associate Professor - Department of Medicine

Dr. Ivan Litvinov
Contact Information
Address: 

捆绑SM社区 Health Centre (MUHC)
1001 Decarie Boulevard,
Montreal, Qc, H4A 3J1

Phone: 
(514) 934-1934 ext. 76140
Email address: 
ivan.litvinov [at] mcgill.ca
Current research: 

Keywords: Skin Cancer; Sun protection; Melanoma; Retrotransposons; Gene-Environnement Interaction; Meiomitosis; Genomic Instability; Retionid Resistance

Skin cancer is more common than all other malignancies combined. According to the American Academy of Dermatology, approximately ~5 million skin cancers are treated each year in the United States alone. It is estimated that ~1/4 Canadians will be affected by a skin cancer in their lifetime and the incidence of these malignancies is increasing. Cutaneous melanoma is responsible for 80% of skin cancer deaths and is the 8th most diagnosed cancer in Canada.

While my lab studies the molecular pathogenesis of skin cancer, a large portion of my team is working on patient public involvement (PPI) research with the goal of instilling safe sun exposure habits in Canadian youth ().

Fair complexion, ultraviolet (UV) exposure and history of sunburns remain critical risk factors for melanoma/skin cancers. Despite extensive knowledge on UVRs detrimental impact, many still fail to implement sun protection/sun avoidance. Hence, promoting sun protection is vital to decrease individual risk of melanoma/skin cancers. We have mapped the incidence of melanoma across Canada by postal code (), described how weather/environment impacts risk of melanoma incidence (), conducted surveys (quantitative) and focus groups (qualitative) to understand risk factors and beliefs/attitudes driving high risk sun exposure behaviors in Canada (; ; ). We also assessed melanoma mortality-to-incidence rate of melanoma across Canada (). We defined the 鈥渟unscreen paradox鈥 whereby increased sunscreen use is correlated with augmented sun exposure and higher rates of skin cancer, leading to a deceptive sense of security (). Our team is using validated patient questionnaires and focus groups to assess melanoma risk, knowledge and protective behavior in select high- vs. low-incidence regions to establish baseline understanding, why certain areas may have higher incidence of this malignancy. We are working with patient partners to develop gender-specific and geographic region-specific recommendations to help change sun exposure practices. We are also actively studying gene-environment interaction to understand how genetic risk in specific regions leads to skin cancer development ().

In the lab we are studying pathogenesis of skin cancers. Genomic instability is a fundamental defining characteristic of cancer that is essential for disease initiation and progression. A critical mechanism that could promote genomic instability is based on the ectopic re-expression of germ cell proteins by cancer cells that could drive cancer meiomitosis, a term describing the clashing of mitosis and meiosis machineries during the cell cycle. Hundreds of proteins expressed by germ and cancer cells have been termed Cancer/Testis antigens (CTAs), which include meiosis-specific CTAs (meiCT). A number of meiCT genes, including HORMAD1, have been shown to be strongly expressed in highly genomically unstable cancers with poor prognoses, suggesting a role in DNA damage/repair processes. MeiCT genes are of particular interest for oncogenesis as they possess chromosome modulating potential due to their inherent activities and may promote genomic instability. Also, in the skin narrow band ultraviolet B (NB-UVB) is has been shown by us and others to trigger LINE-1 reactivation. LINE-1 constitutes ~17% of human genome, has played important evolutionary role. Reactivation of this retrotransposon may result in deleterious effects leading to DNA damage, cellular senescence and photoaging.

Our team is studying the function of ectopically expressed CT genes and reactivation of retrotransposons in these malignancies highlighting the importance of HORMAD1 and LINE-1 in promoting/mediating genomic instability (; ) Our team also defined the function of the ectopically expressed PRAME in KC demonstrating its role in inhibiting retinoid responses and subsequent cell differentiation. We are investigating the molecular mechanism of HORMAD1, PRAME and LINE-1 reactivation and its impact on the carcinogenesis of skin cancers and how HORMAD1 and PRAME pathways could be targeted for clinical benefit.

Selected publications: 

Richie Jeremian, Alexandra Malinowski, Yuliya Lytvyn, Jorge R. Georgakopoulos, Anastasiya Muntyanu, Asfandyar Mufti, Philippe Lefran莽ois, Jensen Yeung, Ivan V Litvinov. 鈥淪kin photoaging following sun exposure is associated with decreased epigenetic and biological age and correlates with basal cell carcinoma phenotype.鈥 Br J Dermatol. 190(4):590-592. doi: 10.1093/bjd/ljad527

Fadi Touma, Marine Lambert, Amelia Mart铆nez Villarreal, Jennifer Gantchev, Brandon Ramchatesingh and Ivan V. Litvinov. 鈥淭he Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence.鈥 Biomedicines 11(11):3017. doi: 10.3390/biomedicines11113017.

Richie Jeremian, Pingxing Xie, Misha Fotovati, Philippe Lefran莽ois, Ivan V. Litvinov. 鈥淕ene-Environment Analyses in a UK Biobank Skin Cancer Cohort Identifies Important SNPs in DNA Repair Genes That May Help Prognosticate Disease Risk鈥 Cancer Epidemiol Biomarkers Prev 32(11):1599-1607. doi: 10.1158/1055-9965.EPI-23-0545

Jennifer Gantchev, Julia Messina-Pacheco, Amelia Mart铆nez Villarreal, Brandon Ramchatesingh, Philippe Lefran莽ois, Pingxing Xie, Laetitia Amar, Hong Hao Xu, Keerthenan Raveendra, Daniel Sikorski, Daniel Josue Guerra Ordaz, Raman Preet Kaur Gill, Marine Lambert, Ivan V. Litvinov. 鈥淓ctopically Expressed Meiosis-Specific Cancer Testis Antigen HORMAD1 Promotes Genomic Instability in Squamous Cell Carcinomas.鈥 Cells 12(12):1627. doi: 10.3390/cells12121627.

Domenico Arcuri, Mohammed Kaouache, Fran莽ois Lagac茅, Denis Sasseville, Ivan V. Litvinov. 鈥淎 case-control pharmacovigilance study of TNF-alpha inhibitors and interleukin inhibitors on tuberculosis, Candida, lymphoma and suicidality using the FAERS database (2014-2020)鈥 J Am Acad Dermatol 89(3):619-621. doi: 10.1016/j.jaad.2023.05.041

Anastasiya Muntyanu, Vladimir Nechaev, Elena Pastukhova, James Logan, Elham Rahme, Elena Netchiporouk, Andrei Zubarev, Ivan V. Litvinov. 鈥淩isk factors and communities disproportionately affected by cervical cancer in the Russian Federation: A national population-based study.鈥 Lancet Reg Health Eur 20:100454. doi: 10.1016/j.lanepe.2022.100454

Pingxing Xie, Philippe Lefran莽ois, Denis Sasseville, Laurent Parmentier and Ivan V Litvinov, 鈥淎nalysis of multiple basal cell carcinomas (BCCs) arising in one individual highlights genetic tumor heterogeneity and identifies novel driver mutations.鈥 J Cell Commun Signal. 16(4):633-635. doi: 10.1007/s12079-022-00679-x

Jennifer Gantchev, Brandon Ramchatesingh, Melissa Berman-Rosa, Daniel Sikorski, Keerthenan Raveendra, Laetitia Amar, Hong Hao Xu, Amelia Mart铆nez Villarreal, Daniel Josue Guerra Ordaz and Ivan V. Litvinov. 鈥淭ools used to assay genomic instability in cancers and cancer meiomitosis.鈥 J Cell Commun Signal 16(2):159-177. (Jan 2022) doi: 10.1007/s12079-021-00661-z

Ivan V Litvinov, Pingxing Xie, Scott Gunn, Denis Sasseville and Philippe Lefran莽ois. 鈥淭he transcriptional landscape analysis of basal cell carcinomas reveals novel signalling pathways and actionable targets.鈥 Life Sci Alliance. 4(7):e202000651. doi: 10.26508/lsa.202000651.

Jennifer Gantchev, Amelia Mart铆nez Villarreal, Scott Gunn, Monique Zetka, Neils 脴dum, Ivan V. Litvinov. 鈥淭he Ectopic Expression of meiCT Genes Promotes Meiomitosis and May Facilitate Carcinogenesis.鈥 Cell Cycle. 19(8):837-854 (April 2020). doi: 10.1080/15384101.2020.1743902

Philippe Lefran莽ois, Pingxing Xie, Scott Gunn, Jennifer Gantchev, Amelia Mart铆nez Villarreal, Denis Sasseville, Ivan V. Litvinov. 鈥淚n Silico Analyses of the Tumor Microenvironment Highlight Tumoral Inflammation, a Th2 Cytokine Shift and a Mesenchymal Stem Cell-Like Phenotype in Advanced in Basal Cell Carcinomas.鈥 J Cell Commun Signal. 14(2):245-254. doi: 10.1007/s12079-020-00563-6

Research areas: 
Cancer
Immunology
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