Alberto Martin PhD
Professor
Alberto Martin

Contact Info

T: (416) 978-4230
F: (416) 978-1938
Website

Location

St. George Campus
University of Toronto, Medical Sciences Building
1 King's College Circle, Room 7302
Toronto, ON, M5S1A8

Accepting

Grad Students Must First Apply Through Department

Appointments

Associate Chair, Undergraduate Studies, Department of Immunology

Research Interests

Adaptive Immunity, Cancer Immunology, B cells

Dr. Martin also maintains a lab website

Research

B Cells and antibodies

My research focuses in two main areas. My first area of research is to investigate antibody production, with a specific focus on how high-affinity antibodies are generated (i.e. somatic hypermutation), and how antibodies of different classes are produced (i.e. class switch recombination). Both of these processes are necessary for an efficient antibody response. We have recently completed an RNAi screen to identify novel factors that play an essential role in class switch recombination. Work is ongoing to characterize novel factors involved in this process.

Gut microbiota and disease

The second area of research being conducted in my lab relates to colon cancer and inflammatory bowel disease. 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 possibly colorectal cancer. Using an animal model of colorectal cancer (i.e. mismatch repair deficiency), 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? 

Publications and Awards

Recent Publications

2018

C. Li, T. Irrazabal, C. So, M. Berru, L. Du, E. Lam, J. Gommerman, Q. Pan-Hammarström, & Alberto Martin* (2018) The H2B deubiquitinase Usp22 promotes antibody class switch recombination by facilitating non homologous end joining. Nature Communications. Vol 9, p1-12

A. Ling, C. So, M. Le, A. Chen, L. Hung, Alberto Martin* (2018) Double stranded DNA break polarity skews repair pathway choice during intra- and inter-chromosomal recombination. PNAS USA. Vol 115, p2800-2805

B. Green, Alberto Martin, A. Belcheva (2018) Deficiency in the DNA glycosylases UNG1 and OGG1 does not potentiate c-Myc-induced B cell lymphomagenesis. Experimental Hematology, In press.

C. Maisonneuve, T. Irrazabal, Alberto 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, Alberto Martin* (2018) Microbiota and Colon Cancer: Orchestrating neoplasia through DNA damage and immune dysregliation. Encyclopedia of Cancer, 3rd edition. Elsevier, In press

2017

S. Oke, Alberto Martin* (2017) Insights into the role of the intestinal microbiota in colon cancer. Therapeutic Advances in Gastroenterology. In Press

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, Alberto 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. Nat Chem Biol. Vol 13, p317-324

2016

M. Le , D. Haddad , A. Ling, C. Li, C. So, A. Chopra, R. Hu, J. Angulo, J. Moffat, Alberto 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, Alberto 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 & Alberto Martin* (2016) Mismatch Repair and Colon Cancer: Mechanisms and Therapies Explored. Trends in Molecular Medicine. Vol 22, p. 274-289

S. Ramachandran & Alberto Martin* (2016) DNA repair during class switch recombination. Encyclopedia of Immunobiology. Elsevier.

2015

Irrazábal* & Alberto 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, Alberto 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 & Alberto 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, Alberto 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, Alberto 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, Alberto 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, Alberto Martin*(2014) Gut microbial metabolism fuels colorectal cancer in Msh2-deficient hosts. Cell. Vol. 158, p. 288-299.

T. Irrazábal, A. Belcheva, S. Girardin, Alberto Martin* and D. Philpott*(2014) The multifaceted role of the intestinal microbiota in colon cancer. Molecular Cell. Vol. 54, p. 309-20.

Alberto Martin*, R. Chahwan, J.Y. Parsa, M. D. Scharff* (2014) Molecular mechanism of Somatic Hypermutation. Molecular Biology of B Cells. Elsevier.

2013

B. Boulianne, O. Rojas, D. Haddad, A. Zaheen, A. Kapelnikov, T. Nguyen, J. Gommerman*, Alberto Martin*  (2013) AID and Caspase 8 shape the germinal center response through apoptosis. J. Immunology. Vol. 191, p. 5840-47.

 B. Boulianne, M. Le, L. Ward, L. Meng, Alberto Martin*, J. Gommerman* (2013)Lymph Node Germinal Centers form in the absence of Follicular Dendritic Cells, but their maintenance and function requires Lymphotoxin-b Receptor signaling. J. Immunology.  Vol. 191, p. 4521-30.

A. Belcheva, B. Green, A. Weiss, C. Streutker, Alberto Martin* (2013). Elevated incidence of polyp formation in APCMin/+Msh2-/- mice is independent of nitric oxide-induced DNA mutations. PLOS One. Vol. 8(5), e65204.

G. Galicia-Rosas, B. Boulianne, N. Pikor, Alberto Martin, J. Gommerman (2013) Secondary B cell Receptor diversification is necessary for T cell mediated neuroinflammation during Experimental Autoimmune Encephalomyelitis. PLOS One. Vol. 8(4), e61478.

2012

M. Larijani* & Alberto Martin* (2012) The Biochemistry of Activation-Induced Cytidine Deaminase and its physiological functions. Seminars in Immunology. Vol. 40, p. 548-563.

H. Li, R.M. Nepal, Alberto Martin, S.A. Berger (2012). Induction of apoptosis in Eμ-myc lymphoma cells in vitro and in vivo through calpain inhibition. Expt. Hematology. Vol. 40, p. 548-563.

J. Parsa, S. Ramachandran, A. Zaheen, R. Nepal, A. Kapelnikov, A. Belcheva, M. Berru, D. Ronai, Alberto Martin* (2012). Negative supercoiling creates single-stranded patches of DNA that are substrates for AID-mediated mutagenesis. PLoS Genetics. Vol. 8, e1002518.

A. Dancyger, J. King, M. Quinlan, H. Fifield, S. Tucker, H. Saunders, M. Berru, B. Magor, Alberto Martin, M. Larijani (2012). Differences in the enzymatic efficiency of bony fish and human AID are mediated by a single residue in the C-terminus that modulates single-stranded DNA binding. FASEB J. Vol. 26, p.1517-25.

J.H. Fritz, D. McCarthy, N. Simard, O. Lucia Rojas, S. Hapfelmeier, S. Rubino, S. Robertson, M. Larijani, I. Ivanov, Alberto Martin, R. Casellas, D. Philpott, S. Girardin, K. McCoy, A. Macpherson, C. Paige and J. Gommerman (2012).Acquisition of a multifunctional TNF/iNOS-producing IgA+ plasma cell phenotype in the gut. Nature. Vol. 481, p.199-203.

2011

B. Green, A, Belcheva, R.M. Nepal, B. Boulianne, and A. Martin (2011)The mismatch repair pathway functions normally at a non-AID target in germinal center B cells. Blood. Vol. 118, p. 3013-8.

B. Duvvuri, V. Duvvuri, J. Grigull, A. Martin, Q. Pan–Hammarstrom, G.E. Wu, M. Larijani (2011). Altered spectrum of somatic hypermutation in Common Variable Immunodeficiency Disease characteristic of defective repair of AID-induced mutations. Immunogenetics. Vol. 63, p.1-11.

A. Zaheen and A. Martin (2011) Activation induced cytidine deaminase and aberrant germinal center selection in the development of humoral autoimmunities. Amer. J. of Pathology. Vol. 178, p.462-71.

2010

S. Ramachandran, R. Chahwan, R.M. Nepal, D. Frieder, S. Panier, A. Zaheen, D. Durocher, M. Scharff, and A. Martin (2010). The RNF8/RNF168 ubiquitin ligase cascade is required for class switch recombination. Proc Natl Acad Sci USA.Vol. 107, p. 809-814

2009

R.M. Nepal, L. Tong, B. Kolaj, W. Edelmann, A. Martin (2009). Msh2-dependent DNA repair mitigates a unique susceptibility of B cell progenitors to c-myc-induced lymphomas. Proc Natl Acad Sci USA. Vol. 106, p. 18698-703.

D. Frieder, M. Larijani, C. Collins, M. Shulman, A. Martin (2009). The concerted action of Msh2 and UNG stimulates error-prone repair at A:T basepairs in hypermutating B cells. Mol Cell Biol. Vol. 18, p. 5148-57.

A. Zaheen, B. Boulianne, S. Ramachandran, J.Y. Parsa, J.L. Gommerman, A. Martin (2009). AID constrains Germinal Center size by Rendering B cells Susceptible to Apoptosis. Blood. Vol. 114, p.547-554.

 

* Corresponding author

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