SOME NOTABLE PROJECTS
Battling the Most Aggressive Breast Cancer
Inflammatory breast cancer (IBC) is a rare but highly aggressive form of breast cancer. Although it accounts for only 2 - 4% of U.S. breast cancer cases, it contributes to 7% of all breast cancer-related deaths. Our studies addressed two significant issues within IBC research: the mechanisms that drive its rapid progression throughout the body are not well understood, and there is a critical lack of IBC cell lines that recapitulate all of the clinical features of this devastating disease.
Under the mentorship of Dr. Mihaela Skobe at Mount Sinai Hospital in NYC, I led a project that characterized a novel IBC cell line that demonstrated all of its classical clinical features when injected into mice, and identified CCL2 as a critical chemokine in IBC progression (results published in Nature Communications). I also identified a new therapeutic treatment for IBC that inhibits essential pathways for its metastatic spread, and those results will be published this year.
Figure upper panel shows examples of clinical features of IBC, including redness of skin overlaying an IBC tumor, and arrows pointing towards grossly enlarged dermal lymphatic vessels filled with IBC tumor cells. Bottom panel shows treatment efficacy in reducing lymphatic vessel enlargement and metastases. All scale bars = 100uM.
Wild Mice, Climate Change, and Habitat Fragmentation: What Does This Mean for Lyme Disease?
In the late 2000s, the Canadian government embarked on a large initiative to decipher how Canada’s changing environment influences the spread of Lyme disease, and my collaborative role was to conduct an extensive population and landscape genetics analysis of the white-footed mouse, which is the most important reservoir of the bacteria. By learning how the mice moved, we could add power to our predictions on how a Lyme disease outbreak would spread as well.
The mice proved to disperse quite well within agricultural fields, and were fairly competent at crossings roads as well. Large rivers, however, significantly decreased their migration and played an important role in predicting their movements. Just over 20% of the mice captured had ticks attached to them, and combining the mouse dispersal analysis and tick information allowed me to identify important sites of interest for disease management strategies (paper here). My data was then merged into a collaborative project where a climate change model was used to determine the future spread of Lyme disease. Predictions stated that by 2050, Lyme disease will have spread up to 45°N, and that regions located below this latitude will be at high risk for harboring the disease, ticks and white-footed mice (paper here).
Thrilling Results With Those That Trill
The Boreal chorus frog (Pseudacris maculata) and the Western chorus frog (P. triseriata) are two North American species that are very similar in size and coloration, which has created past taxonomic confusion. Through DNA analysis and playing the breeding calls of various chorus frog species, I discovered that the chorus frog species that actually resides in southeastern Canada has been misidentified for decades and is actually the Boreal chorus frog rather than the Western chorus frog (paper here). These findings are important for frog conservation in southeastern Canada, as these misidentified species were already designated as threatened or at risk due to human land use prior to the study.
Due to constant housing development pressures, the remnant populations found within the fragmented habitats in southeastern Canada are constantly in jeopardy. I therefore carried out a population genetics analysis of multiple Boreal chorus frog populations to identify genetically valuable populations. I demonstrated how the fragmentation of their habitats impedes their migration to distant sites and increases their genetic vulnerability (paper here). These two studies combined provided critical information for chorus frog conservation in southeastern Canada.
The Wolves Have Arrived
Mont-Tremblant National Park is southern Quebec’s largest provincial park, comprised of a vast array of wildlife. In the early 2010s, one of the park’s most important conservation issues was the presence of wolves that became habituated to local tourists. To help clarify the identity of the canines found within the territory, I conducted a thorough population genetics analysis to identify the different species of wild canines that resided in Mont-Tremblant National Park at that time. My study identified 14 individual canines, including the eastward expansion of eastern wolves, who were not believed to have migrated east of Ontario yet. My data indubitably confirmed the eastern wolf’s range distribution in Quebec, and strongly suggested that a distinct population of this species occurred within the large territory of Mont-Tremblant National Park (report here). These results had critical implications for eastern wolf conservation management practices across Canada (more information here). (Photo credit: COSEWIC)
DNA Helps and Hinders Investigations
The advent of DNA profiling has helped solve countless of crimes and brought closure to numerous cold cases. Advanced DNA technology now allows minute amounts of genetic material, known as "trace DNA", to yield complete genetic profiles and identify individuals connected to a crime scene or victim. Although this has been extremely advantageous in criminal cases, the enhanced ability to detect trace DNA has also resulted in an increase in DNA profile contaminants originating from crime scene first responders, personnel, laboratory analysts, and their equipment.
My first forensic study introduced a DNA database that eliminates forensic staff DNA contaminants from criminal evidence, while simultaneously incorporating extra measures to protect the staff's personal information. The design of this database significantly increased staff participation and helped resolve criminal cases quicker (paper here).
Next we looked at DNA transfer during the washing of clothes. Defense lawyers have used this argument in criminal cases, however, a large, controlled study was lacking. We determined that the deposition of semen onto clothing, that is then washed with children's underwear in the same load, could yield partial male genetic profiles and transfer some intact spermatozoa onto the underwear. Based on our results, we provide a proposed framework for examining and interpreting male DNA in laundered clothing during sexual abuse investigations (paper here).