Alberto Martin
PhD
Dr. Martin also maintains a lab website
The Martin Research Program
Our overarching research program is devoted towards understanding the role of genes and their interaction with the environment and immunity in various pathological conditions. Our current research interests can be divided into three main areas, each of which is supported by external research funding: The generation of antibody diversification, the molecular mechanisms of cancer development (i.e. emphasis on colon cancer), and the molecular mechanisms of inflammatory bowel disease and metabolic disease.
Research Projects
Generation of antibody diversity in mature B cells
The antigen binding site of antibodies are created in immature B cells by the random assembly of variable (V), diversity (D), and joining (J) segments into one coding exon by a process termed V(D)J recombination. This process creates a very large repertoire of antibodies with different specificities. However, most antibodies that are generated bind to antigens such as viruses and bacteria with low affinity. In order to neutralize and clear pathogens and toxins from the circulation, B-cells must produce and secrete antibodies of higher affinity and of different classes. Following exposure to antigen, the V regions of the antibody genes acquire many base changes that result in antibodies that bind with higher affinities to their respective antigens. This phenomenon is achieved by the somatic hypermutation process. The constant region of the antibody gene encodes the remaining part of the antibody molecule and is responsible for carrying out the effector functions of the antibody. Constant regions, which define the antibody class, can be replaced with other constant regions by the class switch recombination process, thereby changing the antibody effector functions without changing the antigen binding site.
The discovery of the B cell-specific activation-induced cytidine deaminase (AID) gene has resulted in a dramatic leap forward in our understanding of the processes of somatic hypermutation and class switch recombination. Mice and humans deficient in AID are incapable of somatic hypermutation and class switch recombination, while overexpression of AID can induce somatic hypermutation and class switch recombination in most cell types. Thus, AID is the only B cell specific protein that is required for both of these processes. Current work in the laboratory is centered on delineating the molecular mechanisms of the somatic hypermutation and class switch recombination processes including the DNA repair proteins that repair the AID-induced DNA lesions.
The molecular mechanisms of cancer development
Our focus is on uncovering the etiology of colorectal cancer, which is the third most common type of cancer and leading cause of cancer-related deaths. Specific genetic mutations are linked to colorectal cancer development, and mutations in genes involved in mismatch repair are one of the most common types of genetic deficiencies that predispose to this type of cancer. The normal function of mismatch repair is to repair mutations produced during DNA replication. In the absence of mismatch repair, mutations accumulate throughout the genome. However, it is not clear why mismatch repair deficiency leads specifically to an increased risk in developing colon cancer, and our laboratories research focus is aimed at uncovering this mystery.
Although the gut microbiota has beneficial effects to the host, it has also been linked to the development of certain pathological disorders, including inflammatory bowel diseases, and colorectal cancer. Using an animal model of colorectal cancer, we showed that the gut microbiota promotes this disease. While this work seems quite distinct to the work outlined above, the common theme is the mismatch repair system since this DNA repair pathway plays an essential role in somatic hypermutation and class switch recombination as well as in colon cancer. We currently have two questions that are designed to characterize the mouse model of colorectal cancer: (1) which bacterial species and what metabolite is/are promoting the development of colorectal cancer? (2) What is the underlying mechanism by which this occurs?
The molecular mechanisms of inflammatory bowel disease and metabolic disease.
With our overall goal of characterizing genes and their interaction with the environment in various pathological conditions, we have uncovered a gene that regulates both inflammatory bowel disease (IBD) and obesity-associated metabolic disease. Our work is centered on characterising this novel gene product and the mechanism by which it regulates these two conditions.
Recent Publications
2025
P. Barbulescu, M. Wong, L. Baronijan, P. Wang, A. Aderinto, M. Kneussel, A. Martin* (2025) MKLN1-dependent GID4/CTLH E3 ubiquitin ligase complex assemblies are required to support B cell antibody diversification. J. Immunol. In Press.
Y. Feng*, P. Barbulescu, C. Chana, M. Shirdarreh, H. Yang, L. Wu, S. Mamand, M. Kashem, A. Zia, M. Han, J. Tsao, T. Pugh, D. Cescon, D. Schatz, F. Sicheri, A. Martin, R. Pezo* (2025) FAM72A promotes UNG2 degradation and mutagenesis in human cancer cells. Scientific Reports. Vol 15, p. 1-10.
Thakur, Y. Malaise, S. Choudhury, A. Neustaeter, W. Turpin, C. Streutker, J. Copeland, E. Wong, W. Navarre, D. Guttman, C. Jobin, K. Croitoru, A. Martin* (2025) Dietary fibre counters the oncogenic potential of colibactin-producing Escherichia coli in colorectal cancer. Nature Micro. Vol. 10 p. 855-870.
2024
S. Mamand, H. Liu, M. Kashem, A. Martin* (2024) Suppression of Class Switch Recombination to IgA by RASA2 and RASA3 through inhibition of TGF-β signaling. J. Immunol. Vol. 213 p. 1739-1745.
P. Barbulescu, A. Martin* (2024) DNA Repair Factors Involved in Class Switch Recombination Encyclopedia of Immunobiology. Elsevier. In Press.
P. Barbulescu, C. Chana, M. Wong, I. Makhlouf, J. Bruce, Y. Feng, A. Keszei, C. Wong, R. Mohamad-Ramshan, M. Kashem, D. Ceccarelli, S. Orlicky, Y. Fang, H. Kuang, M. Mazhab-Jafari, R. Pezo, A. Bhagwat, T. Pugh, A.C. Gingras, F. Sicheri*, A. Martin* (2024) FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation. Nature Comm. Vol 15:7541, p 1-19.
J. Ridani, P. Barbulescu, A. Martin, J.M. Di Noia (2024) Somatic Hypermutation. Molecular Biology of B Cells 3rd Edition Elsevier.
T. Honjo, M. Reth, A. Radbruch, F. Alt, and A. Martin (2024). Molecular Biology of B cells, 3rd edition Elsevier.
2022
Y. Feng, A. Martin* (2022) Mutagenic repair during antibody diversification: Emerging insights. Trends in Immunology. Vol. 43, p.604-607.
M. Wong, J. Liu, P. Budylowksi, E. Yue, Z. Li, J. Rini, J. Carlyle, A. Zia, M. Ostrowski*, A. Martin* (2022) Convergent CDR3 homology amongst Spike-specific antibody responses in convalescent COVID-19 patients receiving the BNT162b2 vaccine. Clinical Immunol. Vol 237, p.1-11.
Wong, E. Brownlie, K. Ng, S. Kathirgamanathan, B. Yu, B. Merrill, K. Huang, A. Martin, C. Tropini, and W. Navarre (2022) The CIAMIB: a large and metabolically diverse collection of inflammation-associated bacteria from the murine gut. mBio.Vol 13, p.1-18.
2021
Y. Feng, C. Li, J. Stewart, P. Barbulescu, N. Desivo, A. Álvarez-Quilón, R. Pezo, M. Perera, K. Chan, A. Tong, R. Mohamad-Ramshan, M. Berru, D. Nakib, G. Li, G. Kardar, J. Carlyle, J. Moffat, D. Durocher, J. Di Noia, A. Bhagwat, A. Martin* (2021) FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation. Nature. Vol. 600, p. 324-328.
T. Irrazabal, B. Thakur, K. Croitoru, A. Martin* (2021) Preventing Colitis-associated Colon Cancer with antioxidants: A systematic Review. Cell. Mol. Gastro. Hepat. Vol. 4, p. 1177-1197
C. Maisonneuve, D. Tsang, E. Foerster, T. Mukherjee, D. Prescott, I. Tattoli, P. Lemire, D. Winer, S. Winer, C. Streutker, K. Geddes, K. Cadwell, R. Ferrero, A. Martin, S. Girardin, D. Philpott (2021) Nod1 Promotes Colorectal Carcinogenesis by Regulating the Immunosuppressive Functions of Tumor-Infiltrating Myeloid Cells. Cell Reports. Vol. 34, p. 1-18
2020
M. Galati, K. Hodel, M. Gams, S. Sudhaman, T. Bridge, W. Zahurancik, V. Park, A. Ercan, L. Joksimovic, I. Siddiqui, R. Siddaway, M. Edwards, R. de Borja, D. Elshaer, J. Chung, V. Forster, N. Nunes, M. Aronson, X. Wang, J. Ramdas, A. Seeley, T. Sarosiek, G. Dunn, J. Byrd, O. Mordechai, C. Durno, A. Martin, A. Shlien, E. Bouffet, Z. Suo, J. Jackson, C. Hawkins, C. Guidos, Z. Pursell, & U. Tabori (2020) Cancers from Pole mutant mice provide insights into polymerase-mediated hypermutagenesis and immune checkpoint blockade. Cancer Research. Vol 80, p. 5606-5618
Olivieri, T. Cho, A. Álvarez-Quilón, K. Li, M. Schellenberg, M. Zimmermann, N. Hustedt, S. Rossi, S. Adam, H. Melo, A. Margriet Heijink, G. Sastre-Moreno, N. Moatti, R. Szilard, A. McEwan, A. Ling, A. Serrano Benitez, T. Ubhi, G. Brown, F. Cortes-Ledesma., R. Scott Williams, A. Martin, D. Xu and D. Durocher (2020) A genetic map of the response to DNA damage in human cells. Cell. Vol. 182, p. 481-496
A. Ling, M. Munro, N. Chaudhary, C. Li, M. Berru, B. Wu, D. Durocher, A. Martin* (2020) SHLD2 promotes class switch recombination in B cells by preventing large inactivating deletions within immunoglobulin heavy chain loci. EMBO Reports. Vol 21, p. 1-13
Y. Feng, N. Seija, J. Di Noia*, A. Martin* (2020) AID in Antibody Diversification: There and Back again. Trends in Immunology. Vol 41, p. 586-600
T. Irrazabal, B. Thakur, M. Kang, Y. Malaise, C. Streukter, E. Wong, J. Copeland, D. Guttman, W. Navarre, A. Martin* (2020) Limiting Oxidative DNA Damage Reduces Microbial-induced Colitis Associated Colorectal Cancer. Nature Communications. Vol 11, 1802, p.1-14
C. Li, E. Lam, C. Perez-Shibayama, L. Ward, J. Zhang, D. Lee, A. Nguyen, M. Ahmed, E. Brownlie, K. Korneev, O. Rojas, T. Sun, W. Navarre, H. He, A. Martin, B. Ludewig, and J. Gommerman (2020) Early life programming of Mesenteric Lymph Node Stromal Cell Identity by the Lymphotoxin Pathway Regulates Adult Immune Responses. Science Immunology. Vol. 4 p. 1-17
2019
R. Pezo*, M. Wong, and A. Martin* (2019) Gut microbes and immune checkpoint inhibitor-associated toxicities. Therapeutic Advances in Gastroenterology. Vol. 12, p. 1-10
C. So and A. Martin* (2019) DSB structure impacts DNA recombination leading to class switching and chromosomal translocations in human B cells. PLoS Genetics. Vol. 15, e1008101
C. So, S. Ramachandran, A. Martin* (2019) E3 ubiquitin ligases RNF20 and RNF40 are required for DSB repair: evidence for monoubiquitination of histone H2B lysine 120 as a novel axis of DSB signaling and repair. Mol Cell Biol. Vol. 39, e00488-18
B. Thakur, Y. Malaise, A. Martin*. (2019) Unveiling the Mutational Mechanism of the Bacterial Genotoxin Colibactin in Colorectal Cancer. Molecular Cell. Vol 74, p. 227-229
R. Nepal & A. Martin* (2019) Pillars in Immunology: Unmasking the Mysteries of Myc. J. Immunology. Vol 202, p. 2517-2518
2018
C. Li, T. Irrazabal, C. So, M. Berru, L. Du, E. Lam, J. Gommerman, Q. Pan-Hammarström, & A. Martin* (2018) The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non homologous end joining. Nature Communications. Vol 9, 1006, p.1-12
A. Ling, C. So, M. Le, A. Chen, L. Hung, A. Martin* (2018) Double stranded DNA break polarity skews repair pathway choice during intra- and inter-chromosomal recombination. PNAS USA. Vol 115, p2800-2805
S. Nordermeer, S. Adam, D. Setiaputra, M. Barazas, S. Pettitt, A. Ling, M. Olivieri, A. Alvarez Quilon, N. Moatti, M. Zimmermann, S. Annunziato, D. Krastev, A. Sherker, S. Landry, R. Szilard, M. Munro, A. McEwan, T. Goullet de Rugy, Z. Lin, T. Hart, J. Moffat, A. Gingras, A. Martin, H. van Attikum, J. Jonkers, C. Lord, S. Rottenberg, D. Durocher (2018) The Shieldin complex mediates 53BP1-dependent DNA repair. Nature. Vol 560, p117-121
M. Tanaka, J. Fine, C. Kirkham, O. Aguilar, A. Belcheva, A. Martin, T. Ketela, J. Moffat, D. Allan, J. Carlyle (2018) The inhibitory NKR-P1B:Clr-b recognition axis facilitates detection of oncogenic transformation and cancer immunosurveillance. Cancer Research. Vol 78, p3589-3603
G. Galicia, D. Lee, V. Ramaglia, L. Ward, J. Yam, Y. Leung, R. Li, M. Handy, J. Zhang, P. Drohomyrecky, S. Dunn, E. Lancaster, A. Bar-Or, A. Martin, J. Gommerman. (2018) Isotype-switched auto-antibodies are necessary to facilitate CNS autoimmune disease in Aicda-/- and Ung-/- mice. J. Immunology. Vol. 20, p1119-1130
B. Green, A. Martin, A. Belcheva (2018) Deficiency in the DNA glycosylases UNG1 and OGG1 does not potentiate c-Myc-induced B cell lymphomagenesis. Experimental Hematology, Vol 61, p52-58.
C. Maisonneuve, T. Irrazabal, A. Martin, S. Girardin, & D. Philpott (2018) The impact of the gut microbiome on colorectal cancer. Annual Review Cancer Biology. Vol 2, p. 229-249.
T. Irrazabal, A. Martin* (2018) Microbiota and Colon Cancer: Orchestrating neoplasia through DNA damage and immune dysregulation. Encyclopedia of Cancer, 3rd edition. Elsevier, In press.
2017
M. Kang & A. Martin* (2017) Microbiome and colorectal cancer: Unraveling host-microbiota interactions in colitis-associated colorectal cancer development. Seminars in Immunology. Vol 32, p. 3-13.
S. Oke, A. Martin* (2017) Insights into the role of the intestinal microbiota in colon cancer. Therapeutic Advances in Gastroenterology. Vol 10, p. 417-428
K. Bromberg, T. Mitchell, A. Upadhyay, C. Jakob, L. Lasko, C. Li, C. Tuzon, Y. Dai, F. Li, M. Eram, A. Nuber, N. Soni, V. Manaves, M. Algire, R. Sweis, M. Torrent, G. Schotta, C. Sun, M. Michaelides, A. Shoemaker, C. Arrowsmith, P. Brown, V. Santhakumar, A. Martin, J. Rice, G. Chiang, M. Vedadi, D. Barsyte-Lovejoy and W. Pappano (2017) The novel SUV4-20 inhibitor A-196 verifies a role for epigenetics in the maintenance of genomic integrity. Nature Chemical Biology. Vol 13, p317-324
2016
M. Le , D. Haddad , A. Ling, C. Li, C. So, A. Chopra, R. Hu, J. Angulo, J. Moffat, A. Martin* (2016) Kin17 facilitates multiple double-strand break repair pathways that govern B cell class switching. Scientific Reports 6:37215
S. Ramachandran, D. Haddad, C. Li, M. Le, A. Ling, C. So, R. Nepal, J. Gommerman, K. Yu, T. Ketela, J. Moffat, A. Martin* (2016) The SAGA deubiquitination module promotes DNA repair and class switch recombination through DNAPK-mediated gH2AX formation. Cell Reports. Vol. 15, p1554–1565
S. Li & A. Martin* (2016) Mismatch Repair and Colon Cancer: Mechanisms and Therapies Explored. Trends in Molecular Medicine. Vol 22, p. 274-289
2015
Irrazábal* & A. Martin* (2015) T regulatory cells gone bad: An oncogenic immune response against enterotoxigenic B. fragilis infection leads to colon cancer. Cancer Discovery. Vol. 5, p. 1021-1023
A. Belcheva*, T. Irrazábal, A. Martin* (2015) Gut microbial metabolism and colon cancer: Can manipulations of the microbiota be useful in the management of gastrointestinal health. BioEssays. Vol. 37, p. 403-12
A. Belcheva & A. Martin* (2015) Gut microbiota and colon cancer: the carbohydrate link. Molecular Cellular Oncology. Vol 2. p. 1-2
2014
S. Shalhout, D. Haddad, A. Sosin, AT. Holland, A. Al-Katib, A. Martin, A. Bhagwat (2014) Homeostasis in Genomic Uracil Creation and Elimination during Normal B Cell maturation, and loss of this balance during B Cell cancer development. Mol Cell Biol. Vol. 34, p. 4019-32.
K. Johnson-Henry, L. Pinnell, A. Waskow, T. Irrazabal, A. Martin, M. Hausner, P.M. Sherman(2014) Effects of a Short-Chain Fructo-oligosaccharide and Inulin in Caco2-bbe and C57Bl/6 Mice Models of Intestinal Injury. J. Nutrition. Vol. 144, p. 1725-33
F. Soares, I. Tattoli, M. Rahman, S. Robertson, A. Belcheva, D. Liu, C. Streutker, S. Winer, D. Winer, D. Arnoult, A. Martin, D. Philpott, S. Girardin (2014) The mitochondrial protein NLRX1 controls apoptotic cell death in cancer cells. J. Biol Chem. Vol. 289, p.19317-30.
A. Belcheva, T. Irrazabal, S. Robertson, C. Streutker, E. Moriyama, H. Maughan, S. Kumar, B. Green, S. Rubino, R. Pezo, W. Navarre, M. Milosevic, B. Wilson, S. Girardin, W. Edelmann, T. Wolever, D. Guttman, D. Philpott, A. Martin*(2014) Gut microbial metabolism fuels colorectal cancer in Msh2-deficient hosts. Cell. Vol. 158, p. 288-299.
T. Irrazábal, A. Belcheva, S. Girardin, A. Martin* and D. Philpott*(2014) The multifaceted role of the intestinal microbiota in colon cancer. Molecular Cell. Vol. 54, p. 309-20.
* Corresponding author