"I would argue that infectious disease is really a Native issue, almost independent of which organism you work on," said Matt Anderson, Ph.D., an assistant professor at The Ohio State University who is of Eastern Band of Cherokee Indians (EBCI) descent and white. Though environmental science and human genetics are front-of-mind for many Native American scientists (the first because of strong land stewardship traditions and the second because of a history of misuse of Indigenous genetic data), Anderson was drawn to infectious disease. This choice was just as influenced by his Native identity though. Asked about his scientific interests, he comes back repeatedly to Indigenous health disparities. Just as the rates of chronic illnesses like cardiovascular disease are higher in these communities, so too is the prevalence of infectious disease in the few cases where it has been studied. Only with the COVID-19 pandemic is that fact becoming more widely recognized.

Anderson has family on his mother's side enrolled in the EBCI, who originally inhabited land in North Carolina, Georgia, Tennessee and Alabama before being forcibly relocated by the U.S. government. He grew up in Portland, Ore., relatively disconnected from the Native American community, at a time when the city was struggling with gang violence and homelessness. "It was not 'Portlandia' ... you kind of got hit in the face with the repercussions of infectious agents all the time," he recalled. "I really wanted to work in infectious disease because of the experience of seeing what happened with the HIV epidemic in the 80s and into the 90s where I was."

Anderson moved to Wisconsin as an adolescent. It was there that he and his sisters began to explore their Native American heritage and got involved with the Native community. "The process of being involved is really just about being present," he explained.

After receiving his undergraduate degree from the University of Wisconsin, Madison, Anderson went on to pursue his Ph.D. at Stanford University in the laboratory of Dr. John Boothroyd, studying the intracellular, eukaryotic parasite Toxoplasma gondii. The parasite is typically acquired from undercooked infected meat or from cat feces. T. gondii is also amongst a rare group of pathogens that are capable of congenital transmission, being passed by infected mothers to their babies. Though it is one of the world's most common parasites, T. gondii infection is usually asymptomatic in healthy individuals. However, in those with weakened immune systems, it causes toxoplasmosis, a disease characterized by muscle pain, headache and fever. Anderson's interest in the organism stems from the populations most affected by it - before the advent of antiretroviral therapy, T. gondii was one of several parasitic infections that routinely killed AIDS patients. In addition, Indigenous communities have been documented with T. gondii infection rates that are far higher than surrounding non-Indigenous populations.

In the Boothroyd lab, Anderson also tapped into his interest in genetics. Using insertional mutagenesis, he generated T. gondii mutants that had trouble transitioning from tachyzoites (the disease-causing stage that infects muscle and neural tissue) to bradyzoites (the stage that forms dormant cysts within tissues) in vitro. He tracked down the insertion in one such mutant to a gene with homology to pseudouridine synthase (PUS1). Interestingly, mice infected with PUS1 mutants had higher parasite burdens, smaller but more numerous cysts and higher mortality. Anderson thinks that, in vivo, PUS1 may stabilize the tachyzoite stage. He hypothesized that without it, T. gondii has trouble maintaining dormancy, leading to waves of inflammation that eventually overcome the host.

While working on T. gondii in graduate school, Anderson was also supporting a family. Financial hardships meant working a second job and working with department administration to secure housing assistance and health insurance for his family (at the time, Stanford did not offer insurance for the dependents of graduate students). In reference to resources others take for granted, he said, "My personal and in-law extended family had no means to buoy us up. We were on our own."

Unfortunately, equivalent forms of assistance were not available after Anderson graduated and went on to the University of Minnesota for his postdoc in 2010. In the lab of Dr. Judith Berman, he switched to another opportunistic eukaryotic pathogen, Candida albicans. "I wanted to work with an infectious agent that I felt continued to stay relevant to some of the populations that were important to me," he said, referencing HIV/AIDS patients and Indigenous communities. "I also wanted to work with someone who was well established in the field," he explained, refering, at least in part, to the importance of adequate lab funding. "I needed a place that could guarantee me a certain level of stability. I couldn't afford to do a 6-month appointment and then hope I landed a fellowship." 

In those with weakened immune systems, C. albicans yeast can cause a variety of diseases, from mucosal infection (thrush) to systemic and life-threatening bloodstream infection (candidemia). Anderson focused on the telomere-associated (TLO) gene family found in subtelomeric regions of Candida spp. Though the TLO genes were expanded in number in Candida albicans, relative to other Candida species (indicating evolutionary importance), their function was unknown. Based on a conserved transcriptional regulation domain, coupled with variability in other regions, Anderson proposed that the TLO genes were transcriptional regulators specifically expanded in C. albicans to allow the opportunistic pathogen to survive in a variety of host niches. Indeed, Anderson was able to follow the evolution of this gene family during more than 4000 generations in cell passage, capturing mechanistic detail of how specific TLO family members were further duplicated or deleted over time.

In 2013, Berman moved her lab out of the country, and Anderson moved to Dr. Richard Bennett's lab at Brown University to finish his postdoc. In Bennett's lab, Anderson expanded beyond the TLO gene family to look at the genotypic and phenotypic diversity between patient isolates of C. albicans. This intraspecies diversity, as well as the functions of the TLO gene family, is a continued focus of his lab at The Ohio State University, which was established in 2016.

Anderson's Native identity and his identity as a scientist intertwine most often in where he chooses to invest his time, from instruction to research to mentorship. He advises other scientists from underrepresented groups to "have a clear plan for [your] future and resist the push and pull of different people drawing [you] away from what [you] want and towards something else." Anderson is involved with several initiatives to build scientific capacity and ensure that Native American communities benefit from scientific research, including the Summer Internship for Indigenous Peoples in Genomics (SING), Indigidata and the Native BioData Consortium (NBDC). He's seen the critical mass of Native geneticists effectively organize and establish autonomy within that field. In contrast, Anderson can name only 4 other Native American, faculty-level microbiologists in the U.S. Raising the point that autonomy and self-determination are critical for Indigenous communities, he said, "Micro needs to catch up."
 

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