Our Faculty

Courses I Teach

• BIOL1105 - Introduction to Cellular and Molecular Biology
• BIOL1105L - Introduction to Cellular and Molecular Biology Laboratory
• BIOL1106 - Introduction to Organismal and Evolutionary Biology
• BIOL2119 - Current Topics in Biological Research
• IDDS2201 - Data Analytics
• MATH0118 - R for Statistics

Publications & Presentations

• Mandell, J., Fisk, J. N., Cyrenne, E., Xu, M., Cannataro, V. L., and Townsend, J. P. “Not only mutations but also tumorigenesis can be substantially attributed to DNA damage from reactive oxygen species in RUNX1::RUNX1T1-fusion-positive acute myeloid leukemia" (2022) Leukemia Publication: https://doi.org/10.1038/s41375-022-01752-5
• Cannataro, V. L., Kudalkar, S., Dasari, K., Gaffney, S. G., Lazowski, H. M., Jackson, L. K., Yildiz, I., Das, R. K., Rothberg, B. E. G., Anderson, K. S., Townsend, J. P. “APOBEC mutagenesis and selection for NFE2L2 contribute to the origin of lung squamous-cell carcinoma" (2022)  Lung Cancer
  Publication: https://doi.org/10.1016/j.lungcan.2022.07.004
• Cannataro, V. L., Mandell, J. D., Townsend, J. P., “Attribution of Cancer Origins to Endogenous, Exogenous,and Preventable Mutational Processes" (2022) Molecular Biology and Evolution. Publication: https://doi.org/10.1093/molbev/msac084
• Qing, T., Mohsen, H., Cannataro, V. L., Marczyk, M., Rozenblit, M., Foldi, J., Murray, M. F., Townsend, J. P.,Kluger, Y., Gerstein, M., Pusztai, L. (2022) “Cancer relevance of human genes" Journal of the National Cancer Institute. Publication: https://doi.org/10.1093/jnci/djac068
• *Claus, E. B. and *Cannataro, V. L., Gaffney S. G., Townsend, J. P. (2022) “Environmental and sex-specific molecular signatures of glioma causation” Neuro-Oncology. Publication: https://doi.org/10.1093/neuonc/noab103
  * Denotes co-first-authors and equal contributions
• Tan, C., Mandell, J. D., Dasari, K., Cannataro, V. L., Alfaro-Murillo, J. A., Townsend, J. P. (2021) “Heavy mutagenesis by tobacco leads to lung adenocarcinoma tumors with KRAS G12 mutations other than G12D, leading KRAS G12D tumors—on average—to exhibit a lower mutation burden" Lung Cancer Publication: https://doi.org/10.1016/j.lungcan.2021.10.008
• Klein, M. I., Cannataro, V. L., Townsend, J. P., Newman, S., Stern, D. F., Zhao, H. (2021) “Identifying Modules of Cooperating Cancer Drivers" Molecular Systems Biology
  [Publication: https://doi.org/10.15252/msb.20209810]
• Turken, N., Cannataro, V. L., Geda, A., Dixit, A. (2020) “Nature Inspired Supply Chain Solutions: Definitions, Analogies, and Future Research Directions" International Journal of Production Research [Publication: https://doi.org/10.1080/00207543.2020.1778206]
• Lu, L., Gaffney, S. G., Cannataro, V. L., Townsend, J. P. (2020) “Transfer RNA methyltransferase gene NSUN2 mRNA expression modifies the effect of T cell activation score on patient survival in head and neck squamous carcinoma" Oral Oncology [Publication: https://doi.org/10.1016/j.oraloncology.2019.104554]
• Yang, A., Cannataro, V. L., Townsend, J. P. (2020) “Re: Ming-Jun Shi, Xiang-Yu Meng, Philippe Lamy, et al. APOBEC-mediated Mutagenesis as a Likely Cause of FGFR3 S249C Mutation Over-representation in Bladder Cancer. Eur Urol 2019;76:9–13" European Urology
  [Publication: https://doi.org/10.1016/j.eururo.2019.08.018]
• Somarelli, J. A., Gardner, H., Cannataro, V. L., Gunady, E. F., Boddy, A. M., Johnson, N. A., Fisk, J. N., Gaffney, S. G, Chuang, J. H., Shend, L., Ciccarelli, F. D., Panchenko, A.R., Megquier, K., Kumar, S., Dornburg, A., DeGregori, J., Townsend, J. P. (2019) “Molecular biology and evolution of cancer: from discovery to action" Molecular Biology and Evolution [Publication: https://doi.org/10.1093/molbev/msz242]
• Cannataro, V. L. and Townsend, J. P. (2019) "Wagging the long tail of drivers of prostate cancer" PLOS Genetics [Publication: https://doi.org/10.1371/journal.pgen.1007820]
• Cannataro, V. L., Gaffney, S. G., Sasaki, T., Issaeva, N., Grewal, N. K. S., Grandis, J. R., Yarbrough, W. G., Burtness, B., Anderson, K. S., and Townsend, J. P. (2019) "APOBEC-induced mutations and their cancer effect size in head and neck squamous cell carcinoma" Oncogene [Publication: https://doi.org/10.1038/s41388- 018-0657-6]
• Cannataro, V. L., Gaffney, S. G., Townsend, J. P. (2018) "Effect sizes of somatic mutations in cancer" Journal of the National Cancer Institute [Publication: https://doi.org/10.1093/jnci/djy168]
• Cannataro, V. L. and Townsend, J. P. (2018) "Neutral theory and the somatic evolution of cancer" Molecular Biology and Evolution [Publication: https://doi.org/10.1093/molbev/msy079]
• Wilkins, J., Cannataro, V.L., Shuch, B., Townsend, J.P. (2018) "Analysis of mutation, selection, and epistasis: an informed approach to cancer clinical trials" Oncotarget [Publication: https://doi.org/10.18632/oncotarget.25155]
• Cannataro, V. L., Gaffney, S. G., Stender, C., Zhao, Z., Philips, M., Greenstein, A. E., Townsend, J. P. (2018) "Heterogeneity and mutation in KRAS and associated oncogenes: evaluating the potential for the evolution of resistance to targeting of KRAS G12C" Oncogene [Publication: https://doi.org/10.1038/s41388-017-0105-z]
• Cannataro, V. L., McKinley, S.A., St. Mary, C.M. (2017) "The Evolutionary Trade-off Between Stem Cell Niche Size, Aging, and Tumorigenesis" Evolutionary Applications, 10:590:602. [Publication: https://doi.org/10.1111/eva.12476]
• Gulbudak, H., Cannataro,V. L., Tuncer, N., Martcheva, M. (2017) " Vector-Borne Pathogen and Host Evolution in a Structured Immuno-Epidemiological System" Bulletin of Mathematical Biology 79:325. [Publication: https://doi.org/10.1007/s11538-016-0239-0]
• Tuncer, N., Gulbudak, H., Cannataro, V. L., Martcheva, M. (2016) "Structural and practical identifiability issues of immuno-epidemiological vector-host models with application to Rift Valley Fever" Bulletin of Mathematical Biology 78:1796. [Publication: https://doi.org/10.1007/s11538-016-0200-2]
• Cannataro, V. L., McKinley, S. A., St. Mary, C. M. (2016) "The Implications of Small Stem Cell Niche Sizes and the Distribution of Fitness Effects of New Mutations in Aging and Tumorigenesis" Evolutionary Applications 9:4. [Publication: http://dx.doi.org/10.1111/eva.12361]
• Ferguson, J. M., Langebrake, J., Cannataro, V. L., Garcia, A. J., Hamman, E. A., Martcheva, M., Osenberg, C. W. (2014) "Optimal sampling strategies for detecting zoonotic disease epidemics" PLOS Computational Biology 10:6 [Publication: https://doi.org/10.1371/journal.pcbi.1003668]
• Cox-Paulson, E., Cannataro, V. L., Gallagher, T., Hoffman, C., Mantione, G., Mcintosh, M., Silva, M., Vissichelli, N., Walker, R., Simske, J., Ono, S. and Hoops, H. (2014) "The minus-end actin capping protein, UNC-94/tropomodulin, regulates development of the Caenorhabditis elegans intestine." Developmental Dynamics 243:6 [Publication: http://dx.doi.org/10.1002/dvdy.24118]

Technical Reports: 

• Kaznatcheev, A., Grimes, D. R., Velde, R. V., Cannataro, V. L., et al. "Dark selection for JAK/STAT-inhibitorresistance in CMML" [https://doi.org/10.1101/211151]
• Hanson, S., Grimes, D. R., Taylor-King, J. P., Cannataro, V. L., Bauer, B., Warman, P. I., Frankenstein, Z., Kaznatcheev, A., Bonassar, M. J., Motawe, Z. Y., Lima, E. A. B. F., Kim, S., Davila, M. L., Araujo, A. "Toxicity Management in CAR T Cell Therapy for B-ALL: Mathematical modelling as a new avenue for improvement" [http://dx.doi.org/10.1101/049908]

Recent presentations and invited talks:

• Cannataro, V. L. “Attribution of cancer origins to endogenous, exogenous, and preventable mutational processes" American Association for Cancer Research, Cancer Evolution Working Group Seminar Series Invited Talk, Virtual, Fall 2021
• Cannataro, V. L., Mandell, J. D., Townsend, J. P., “Mutation and selection in tumors: the attribution of cancer origins to endogenous, exogenous, and actionable mutational processes" Society for Molecular Biology & Evolution: 2021 conference Poster presentation; conference held virtually, Summer 2021
• Cannataro, V. L., Gaffney, S. G., Townsend, J. P., "Effect sizes of somatic mutations: the selective advantage that each mutation confers to cancer cells" Evolution 2019 Oral presentation, Providence, Rhode Island, Summer 2019
• Claus E. B., Cannataro V. L., Gaffney S. G., Townsend J. P., Sex Specific Molecular Signatures of Glioma Causation Brain Tumor Epidemiology Consortium. Oral presentation, Los Angeles, California, Spring 2019
• Cannataro, V. L., Gaffney, S. G., Townsend, J. P., "The effect sizes of somatic mutations in cancer " Yale Cancer Center Annual Retreat Poster presentation, Yale University, New Haven, CT, Spring 2019Received the 2019 Scientific Retreat Best Poster Award in Basic Research & Computational Science.
• Cannataro, V. L., Gaffney, S. G., Townsend, J. P., "Effect sizes of somatic mutations: the selective advantage that each mutation confers to cancer cells " Society for Molecular Biology & Evolution: Satellite meeting on the Molecular Biology and Evolution of Cancer Oral presentation, Yale University, New Haven, CT, Spring 2019
• Cannataro, V. L., Gaffney, S. G., Townsend, J. P., "The effect sizes of somatic mutations in cancer and their application in predicting resistance to chemotherapy " Evolution 2018 Poster presentation, Montpellier, France, Summer 2018
• Cannataro, V. L., Gaffney, S. G., Townsend, J. P., "Effect sizes of somatic mutations in cancer" First Annual Yale Cancer Center Trainee Colloquium. Poster presentation, Yale University, New Haven CT, Summer 2018
• Cannataro,V.L.,Gaffney,S.G.,Stender,C.,Zhao,Z.,Philips,M.,Greenstain,A.,Townsend,J.P.,"Mutation, selection, and the targeting of oncogenic KRAS G12C" International Society for Ecology and Evolution of Cancer. Oral presentation, Arizona State University, Tempe AZ, Fall 2017.
• Cannataro,V.L.,Gaffney,S.G.,Stender,C.,Zhao,Z.,Philips,M.,Greenstain,A.,Townsend,J.P.,"Mutation, selection, and the targeting of oncogenic KRAS G12C" International Symposium on Molecular Evolution and Medicine. Oral presentation, Temple University, Philadelphia PA, Summer 2017.
• Cannataro, V. L., Gaffney, S. G., Stender, C., Zhao, Z., Philips, M., Greenstain, A., Townsend, J. P., "The like- lihood of heterogeneity or additional mutation of KRAS amino acid 12 to compromise therapeutic targeting of oncogenic KRAS G12C" Society for Molecular Biology and Evolution Conference. Poster presentation, Austin TX, Summer 2017.
• Cannataro, V. L., Stender, C., Zhao, Z., Greenstain, A., Townsend, J. P., "The likelihood of heterogeneity or additional mutation of KRAS amino acid 12 to compromise therapeutic targeting of oncogenic KRAS G12C" Integrated Mathematical Oncology Workshop 6: Resistance. Poster presentation, Moffitt Cancer Center, Tampa FL, Fall 2016

Research Focus

Every second, hundreds of thousands of our cells die. Don't worry, we are made up of about 30 trillion cells, and the cells that die are replaced by others that divide. However, DNA replication is not perfect, and mutations accumulate in continually dividing cell lineages. Some of these mutations alter a cell's ability to survive and reproduce. Certain lineages of cells may be naturally selected to survive at the expense of others. Over time, the populations of cells in our bodies evolve.

Most of my research revolves around this evolution. How do mutations change the survivability and replicative potential of our own cells? What is this distribution of these mutational effects, i.e., what proportion of mutations decrease or increase cell division? How do these changes eventually result in tumor formation, cancer, and aging? And the myriad of questions that have been coming up along the way.
Some of my research takes a "Top-Down" approach, where we use genomic data and theory from population genetics to infer the dynamics within tumors and tissues. For instance, we recently developed a method to calculate the selection intensity for the substitutions found in tumors. We calculated the intensity by which mutational variants were naturally selected to persist and survive for all recurrent mutations detected in 22 different cancer types, spanning over 10,000 tumors that underwent DNA sequencing. This metric ranks the relative division and survival benefit conferred to cancer cells by the genetic variants driving tumor growth and cancer progression and thus is an extremely important metric to quantify when prioritizing basic research and clinical decision making. This metric, and the parameters we calculate in its derivation, are also useful in predicting what mutations will both occur and drive resistance to chemotherapy-as we demonstrated in another study investigating mechanisms of resistance to a novel chemotherapy.

Every second, hundreds of thousands of our cells die. Don't worry, we are made up of about 30 trillion cells, and the cells that die are replaced by others that divide. However, DNA replication is not perfect, and mutations accumulate in continually dividing cell lineages. Some of these mutations alter a cell's ability to survive and reproduce. Certain lineages of cells may be naturally selected to survive at the expense of others. Over time, the populations of cells in our bodies evolve.
Most of my research revolves around this evolution. How do mutations change the survivability and replicative potential of our own cells? What is this distribution of these mutational effects, i.e., what proportion of mutations decrease or increase cell division? How do these changes eventually result in tumor formation, cancer, and aging? And the myriad of questions that have been coming up along the way.
Some of my research takes a "Top-Down" approach, where we use genomic data and theory from population genetics to infer the dynamics within tumors and tissues. For instance, we recently developed a method to calculate the selection intensity for the substitutions found in tumors. We calculated the intensity by which mutational variants were naturally selected to persist and survive for all recurrent mutations detected in 22 different cancer types, spanning over 10,000 tumors that underwent DNA sequencing. This metric ranks the relative division and survival benefit conferred to cancer cells by the genetic variants driving tumor growth and cancer progression and thus is an important metric to quantify when prioritizing basic research and clinical decision making. This metric, and the parameters we calculate in its derivation, are also useful in predicting what mutations will both occur and drive resistance to chemotherapy-as we demonstrated in another study investigating mechanisms of resistance to a novel chemotherapy.

On the other hand, my colleagues and I also use a "Bottom-Up" approach, where we create mathematical models of cellular dynamics and test assumptions about somatic evolution and its influence on aging and tumor genesis. We recently demonstrated how our bodies accumulate both deleterious mutations everywhere (gradual aging throughout the body) and also rare mutations of large effect that increase cellular fitness (localized areas of increased cellular fitness, i.e. a tumor) by modeling the dynamics of healthy tissue under biologically plausible distributions of mutational "hits". This work raised the question: Why did evolution select for small stem cell niche population sizes if they permit such extensive mutation accumulation throughout our lifetime? Especially since much of these mutations are deleterious to cellular growth and contribute to aging. We created a mathematical model of the entire intestines and all subpopulations within the crypts and varied the population size of stem cells that replenish the entire tissue. We found that there was a population size of stem cells that minimizes the probability of accumulating mutations necessary to initiate a tumor-populations with higher or lower numbers of cells had a higher probability of tumorigenesis-and we found that this population size matches those measured within organisms. We showed that multicellular organisms face a trade-off between the rate that they age (via the accumulation of mutations deleterious to cellular fitness) and the rate that they succumb to cancer (via the accumulation of mutations beneficial to cellular fitness), and it seems that the architecture of the intestines was selected to minimize the rate of cancer, at the expense of aging.

For more information, please see my website here: https://vcannataro.com/research/multicellularity-and-evolution/