B.S., Biochemistry (with honors), Mathematics minor - SUNY Geneseo
Honors thesis title: TMD-1/tropomodulin Regulates Intestinal Shape and Volume During Development in C. elegans
Ph.D., Zoology - University of Florida Dissertation title: The Influence of Tissue Architecture on Somatic Tissue Evolution, Homeostasis, Aging, and Cancer
I am a biologist interested in the evolution within us. I use mathematical modeling, simulations, and bioinformatics to understand the evolution occurring within our bodies everyday-how mutations occur, compete, and accumulate within our tissues-and how these dynamics contribute to aging and cancer. I also develop methods and software to analyze large datasets, such as DNA sequences from healthy tissues and tumors, so that we can unravel the evolutionary dynamics behind the processes driving cancer.
Academic Appointments:
What I Love About Emmanuel:
I love how students have the opportunity to truly engage with both aspects of "science"-science as a body of knowledge and science as the toolkit used to unlock that knowledge. Whether it is using advanced research techniques to pinpoint potential novel tuberculosis therapies in their freshman biology class laboratory, or actively taking part in all aspects of the scientific research process in collaboration with a faculty member, or even venturing just outside campus to take advantage of the internships offered throughout Boston, the line between "Student" and "Scientist" is often blurred at Emmanuel College. Importantly, these research opportunities are pursued in tandem with a liberal arts education relevant to the 21st-century.
Technical Reports:
Recent presentations and invited talks:
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/
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