• Research Projects

    The Maley Laboratory is researching fundamental concepts in neoplastic progression, the processes by which normal tissue becomes cancerous, for the purposes of developing better methods for cancer prevention and therapy. We are applying evolutionary biology, ecology, computational biology and genetics to the understanding of these problems. We are interested in all aspects of evolution in cancer, including the evolution of cells within tumors and normal tissues (“ somatic evolution“) as well as the selective effects of cancer on the evolution of multicellular organisms.

    Neoplastic Progression

     

     

     

    The Evolution of Neoplastic Progression and Cancer Prevention

    Carlo Maley and Diego Mallo are researching Barrett's Esophagus

    We study the pre-malignant condition of Barrett's Esophagus in order to understand how cells in tissues evolve into cancer. We also use Barrett's Esophagus to study how our cancer prevention efforts impact the evolution of those cells. We are testing whether tumors that progress to esophageal cancer (adenocarcinoma) have different evolutionary dynamics from those that remain benign. We are also studying how proton pump inhibitors change those evolutionary dynamics.

    Dr. Angelo Fortunato and Diego Mallo are researching breast cancer.

     

    Genomic and microenvironmental intra-tumor heterogeneity in breast cancer

    Intra-tumor heterogeneity drives neoplastic progression. We hypothesize that the degree of intra-tumor heterogeneity in DCIS should predict which tumors are likely to become invasive and metastatic.

     

    This approach required the development of new methods to extract high quality sequencing data from small amounts of DNA extracted from FFPE samples.

     

    We calculated the genetic divergence between the two spatially distinct tumor regions in order to quantify the intra-tumor heterogeneity. We are investigating tumor microenvironment using ecological methods.

     

    Therapeutic Resistance

     

     

     

    Evolving Resistance

    Alex May is researching cancer resistance

     

    The goal of this project is to understand how cancer cells are able to evolve resistance to therapeutic treatments by quantifying the diversity of mutations that confer these abilities using a wide spectrum of cell lines and drug types. Ultimately, we aim to develop an assay that can be used to predict the emergence of these mutations, thereby providing researchers with a tool that can prioritize candidate drugs before they reach the lengthy clinical approval process.

    Adaptive Therapy

    Carlo Maley, Amy Boddy, and Athena Aktipis are researching adaptive therapies.

    We are working with Bob Gatenby at the Moffitt Cancer Center to explore adaptive therapy. This is a strategy for preventing therapeutic resistance in cancers from getting out of control. Rather than trying to eradicate the tumor, we adapt the dose to the tumor dynamics, increasing the dose if it grows but reducing the dose if it shrinks, with the goal of keeping the tumor a stable size - indefinitely.

    Peto's Paradox

     

     

    What Can We Learn from Large Animals?

    Dr. Marc Tollis is researching elephants and whales

     

    We are investigating the molecular evolution of tumor suppressor genes, proto-oncogenes, and regulatory regions in the genomes of African and Asian elephants (Loxodonta africana and Elephas maximus) as well as available whale genomes to understand how these species are able to avoid cancer.

    Valerie Harris is researching bats

    Why bats?

     

    Bats may the key to a unique mechanism of cancer suppression within their genomes! Bats are an extremely long-lived species with small body sizes and it turns out that they might get cancer at a lower rate than other mammals. Valerie is performing the first survey of cancer rates within wild-caught bat species to determine the frequency of cancer in natura.

    Cancer Rates in Dogs

    Cassandra Balsley is researching cancer rates in dogs

     

    Cassandra is working on collecting cancer rates and inbreeding coefficients for various dog breeds. In addition, she will be identifying specific genes within the canine genome that are involved in cancers and other diseases. She will then compare these regions to those located in other mammalian genomes.

    Macrostomum lignano

     

    Dr. Angelo Fortunato is leading Abbey Colorafi, Emily Ayoub, and Ruby Martinez in a research project on flatworms.

     

    Angelo, Emily, Abbey, and Ruby are researching novel model organisms for cancer research, in particular the flatworm Macrostomum lignano. New model organisms can offer new insights into cancer prevention and development, by studying homologous pathways with human cancers. Currently, they are using X-ray radiation to study cancer development in M. lignano, with the goal of identifying molecular pathways preventing cancer growth.

    Do sponges get cancer?

    Dr. Angelo Fortunato is researching sponges.

     

    Why sponges? Dr. Carlo Maley, the director of the Evolution and Cancer lab says, “In a survey of cancer across species, we noticed that no one had reported cancer in sponges. We don't know if that is because no one has studied cancer in sponges or if sponges are particularly cancer resistant. So we have set out to grow sponges to answer that question.”