Professors Respective Research on Tumor Environment and Skeletal Evolution Gain National Recognition
UMass Dartmouth Biology Assistant Professors Kathryn Kavanagh ("Developmental bias in the evolution of phalanges") and Vanni Bucci ("Emergence of spatial structure in the tumor microenvironment due to the Warburg effect") both had papers published in the high impact scientific journal, "The Proceedings of the National Academy of Science" (PNAS). Professor Kavanagh's paper was coauthored by UMass Dartmouth graduate student Brian Leary. PNAS is one of the world's most-cited multidisciplinary scientific journals, publishing front-line research reports, commentaries, reviews, perspectives, and colloquium papers.
Professor Bucci's paper was a collaborative effort, including contributions from Carlos-Carmona Fontaine and Joao B. Xavier of the Memorial Sloan-Kettering Cancer Center. Professor Bucci is a member of the UMass Dartmouth Center for Scientific Computing and Visualization Research, which promotes internationally-recognized computational research that advances the fields related to Big Data. The paper underlines the importance of the tumor microenvironment in cancer progression, which is a system very difficult to study using standard investigative procedures. Cancer cells in tumors display pronounced metabolic changes. However, the effect of those changes on noncancerous cells near the location of the tumor, or its microenvironment, remains largely unanswered.
Professor Bucci provided the mathematical modeling framework which led to experimental testing of the hypothesis that gradients, such as lactate, emerge due to altered cell metabolism, creating a tumor microenvironment in which tumor associated cells struggle to survive.
The Warburg effect, where glucose is consumed independently of oxygen, leading to high lactic acid production, is arguably the best-known metabolic alteration in cancer. Although these alterations can give growth advantages to cancer cells, it is not clear how they affect healthy cells. The research shows that lactic acid accumulation can impair the survival of tumor-associated cells. Using a co-culture system that mimics the tumor microenvironment, the team showed that a combination of metabolic gradients and differential sensitivity to lactic acid is sufficient for the emergence of the localization of tumor associated cells, where they are known to increase the likelihood of tumor growth and invasion. This suggests that cancer metabolic changes create a microenvironment where tumor cells thrive over other cells. Understanding differences in sensitivity to these alterations may open therapeutic avenues against cancer.
Professor Kavanagh, alongside UMass Dartmouth's Dr. Benjamin Winslow and graduate student Brian Leary, and in collaboration with researchers from Harvard Medical School and Israel's Weizmann Institute of Science, studied the toe bones, or phalanges, of animals in order to test if the developmental process itself can guide evolution. Understanding the "construction rules" of the skeleton can help researchers use the natural tendencies of the skeletal system to facilitate skeletal and joint regeneration in the future.
Using chicken embryos as a model, the team of researchers used small foil barriers placed in the edge of the developing chick digit and found that this interference set up a shift in joint positioning that continued to reverberate during the rest of the digit's development. In contrast, when the barrier was placed in the metatarsal (the major bones of the foot's sole), only the metatarsal was altered with no reverberation into the phalanges.
The final test was then to see if this developmental connectedness influenced evolutionary patterns. The researchers used museum collections and previously published descriptions to measure a large sample of phalanges. Remarkably, the variations were extremely predictable, such that if one knows the size of two phalanges, one can predict the others with confidence. Given this discovery, the researchers propose that the developmental construction rules for phalanges have remained consistent since the first origin of toes.
The research further concludes that the formation of each phalanx bone, rather than being on its own, is part of a larger developmental unit. This ancestral developmental system has been fine-tuned over hundreds of millions of years of vertebrate evolution to work within a very simple set of variations.
UMass Dartmouth's Department of Biology emphasizes field and laboratory opportunities for its students to learn biology while studying living organisms. The department's diverse curriculum provides students with a solid background in fundamental biological principles and practices. It also allows students to take courses geared toward their specific interests. Faculty engage in research at the forefront of their fields, providing students with unparalleled opportunities for research experiences.