I am a Puerto Rican biologist studying the evolution of longevity and healthspan in expectional animals such as bats, elephants, and whales. I use a combination of computational and empirical approaches in my work, using a complete functional genomics pipeline to identify and characterize genetic changes between long- and short-lived species in primary cell culture systems. In addition to my work in aging, I strive to promote transparency, diversity, and inclusivity in STEM, and am actively involved in various outreach and training programs.
My current research focus is the role of genomic stability in longevity differences between species, and the feedback loops between chromatin organization and lifespan. In the Sudmant Lab at UC Berkeley, I use single-cell genomics to study the within-species relationship between chromatin and aging in vivo using mice; and I use primary cell culture samples from various Myotis species of bats to study genomic stabilty and lifespan between species.
Pedagogy and inclusivity are at the heart of my academic program. Science only has meaning when its fruits are widely and openly shared with all; furthermore, science is only beneficial and benevolent when its fruits are available equally to all. As such, I am always seeking more opportunities to reach out and promote STEM to any and all groups and identities!
PhD & MSc in Human Genetics, 2020
University of Chicago
BSc in Biology, Molecular Genetics, 2015
University of Rochester
BA in Chemistry, 2015
University of Rochester
Bats are extraordinarily long-lived relative to other mammals; among them, Myotis lucifugus is one of the longest-lived bats. While M. lucifugus and other closely-related species of bats have been the focus of research for a long time, there have been no reported cases of cancer in the literature - despite their long lifespan - suggesting that they have a low lifetime risk of cancer. In this bat, we find that there is a duplication of the TP53-WRAP53 locus, which is the only such known duplication among sequenced species. The two loci show active transcription both in vivo and in vitro in primary fibroblasts, suggesting that they are both functional. The responses to DNA damage response in M. lucifugus relative to its closest relatives is reminiscient of the effects of a TP53-WRAP53 duplication in transgenic mouse models, suggesting that this duplication may play an important role in mediating the cancer resistance of M. lucifugus.
While body size and lifespan directly impact an individual’s cancer risk within species, we see no such correlation when comparing cancer risk between species - a surprise that is known as Peto’s Paradox. While there are many ways that Evolution can resolve this paradox, gene duplication stands out as a particularly parsimonious solution to the problem. Inspired by previous test cases where a tumor suppressor gene duplication was found in a large, long-lived species - such as in elephants - we sought to test whether or not tumor suppressor duplicates are especially enriched among duplicated genes in large Atlantogenatans. We find that tumor suppressor duplicates are present in all Atlantogenatan genomes, and occured throughout the tree. Tumor suppressor duplicates in Elephants show functional transcription, suggesting that these duplicates have preserved a functional role, and may have permitted the sudden increases in body size we observe throughout Atlantogenata.
Based on emperical studies of humans, mice, and various other species, an individual’s cancer risk is directly proportional to their cell count (body size) and lifespan. This leads to a theoretical prediction that large and/or long-lived species would possess a higher predisposition to cancer compared to smaller, shorter-lived species; compounding this risk is the fact that body size and lifespan are strongly correlated. However, in a phenomenon known as Peto’s Paradox, cancer risk between species does not correlate with either their body sizes or lifespans. This implies that enhanced cancer resistance mechanisms must co-evolve with increases in body size and lifespan; however, there are many ways this can come about. Rather than reinventing the wheel, species can carry an increased load of cancer risk by increasing the number of wheels they have. My thesis focuses on the role tumor suppressor gene duplications play in Peto’s Paradox: Chapter 1 explores whether or not tumor suppressor genes are especially enriched among duplicated genes in large, long lived species, while Chapters 2 and 3 functionally characterize two such duplications. Overall, my work here highlights the vital role that tumor suppressor gene duplicates play in lowering the cancer risk of large, long-lived species, while also highlighting new questions for future work, especially regarding antagonistic pleitropy and growth-suppression paradoxes with these duplicates.
Larger organisms with increased cell counts have a theoretically increased risk of cancer; the observation that larger species do not seem to have an increased cancer risk in contradiction to the patterns observed between members within species is known as Peto’s Paradox. ere, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto’s paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions. LIF6 is transcriptionally upregulated by TP53 in response to DNA damage and translocates to the mitochondria where it induces apoptosis.