Position title: Assistant Professor, Department of Pediatrics
M.D., Ph.D. from the University of Iowa
My mission is to improve the prevention, diagnosis, and management of birth defects and deficits associated with congenital infections. This mission began in 2016, when the beginning of my pediatric infectious diseases fellowship coincided with the advent of the Zika virus pandemic. I had just started a research period in the laboratory of Dr. David O’Connor at UW-Madison when reports about an epidemic of babies born with microcephaly appeared in newspapers. Even more alarming was that some early studies had identified RNA from Zika virus, a mosquito-borne virus, in these infants. My mentor was an expert in developing translational macaque models for viral infections and took this opportunity to establish the first macaque model of Zika virus infection, first in nonpregnant animals (PMID: 27352279), then in pregnant animals (PMID: 28542585). I wrote the animal protocols for these transformative studies, and assisted in developing the experimental design for all the macaque work. I wrote about the first case of fetal demise and ocular defects that occurred in a macaque model (PMID: 29381706), which was a harbinger of the severe outcomes seen in prenatal human Zika virus infection. This experience was so exciting that I knew I wanted to continue working at the interface of virology and clinical diseases with translational nonhuman primate models. In addition to developing the skillset needed to develop translational macaque models of disease, I also developed the skillset needed to quantitatively measure antibody responses to viral infections.
There is a spectrum of disease in infants with prenatal Zika virus infection, ranging from birth defects (microcephaly, contractures, ocular abnormalities) apparent at birth, to neurodevelopmental deficits manifesting in early childhood, and to children who appear healthy. My current research focuses on filling the knowledge gap of why some children have more severe outcomes than others. Learning why some children are less affected may provide targets for effective interventions and therapies. My first goals as a new assistant professor were to develop a translational macaque model for studying deficits during childhood and to define humoral immune correlates of protection. At the same time that I was developing my research portfolio, I also established my laboratory and started mentoring trainees. My priority was to foster an environment of feedback, support, inclusivity, and reproducible science in my laboratory. I accomplished this by taking seminars to develop my mentoring skills, planning regular meetings with my trainees, providing regular feedback, and supporting biannual lab personnel gatherings. With my new team in place, I adapted the comprehensive battery of ocular, hearing, brain imaging, and developmental tests that human infants receive to evaluate for birth defects associated with congenital Zika virus infection, to the pregnant macaque model established during my postdoctoral training. My training as a physician was critical to my task of establishing a team of clinical experts from the UW-Madison campus to perform this comprehensive testing battery. I determined that it was indeed feasible to quantitatively define hearing, vision, brain volumes, and neonatal development in Zika virus-exposed infant macaques with my first senior author manuscript (PMID: 33091010). I knew this would be an important paper so I intentionally took the senior author role and mentored a new graduate student in my colleague’s lab who worked this project as a research technician as the first author. After this translational model was established, I applied this model to address to key questions by partnering my colleague Dr. Karla Ausderau in the Kinesiology Department with an R01 award. Our trans-disciplinary collaboration started during the work on my first senior author manuscript when we found that we both had the same goal of improving long term developmental outcomes in children. With backgrounds in pediatrics and occupational therapy, our collective clinical experiences pushed our science to translate back to the clinical realm.
One of the first questions we addressed was whether a history of maternal Dengue virus infection would worsen prenatal Zika virus infection outcomes. Dengue virus and Zika virus are co-endemic, closely related viruses, and their antibodies cross-react, leading to worse Zika virus disease outcomes in some cellular and animal models. We determined that infant macaques born to dams with prenatal Zika virus infection and pre-existing Dengue virus immunity had worse visual tracking skills in the neonatal period, compared to infants with only prenatal Zika virus exposure (PMID: 34578459). Worse visual tracking skills may have cascading effects for other developmental milestones later in childhood, such as gait abnormalities, social interaction limitations, and fine motor deficits. Because my ultimate goal is to improve outcomes of children with congenital Zika infection, I applied results from this preclinical model to think more broadly about what this means for human infants. These early developmental changes we saw in infancy could be the early warning signs used to identify children for physical therapy to improve their developmental outcomes. The promise of improving outcomes is what is motivating me to search for early warning signs of developmental deficits in childhood by defining hearing, vision, and brain structure patterns throughout infancy and childhood. Some of these differences in neurodevelopmental outcomes may be due to different maternal antibody responses and ability to control the virus infection, so I am also elucidating the antibody immune correlates of protection for these infants. My current research projects are poised to make transformative changes in the long-term developmental outcomes of congenital Zika virus infection.
The future of my research program is cemented within my mission, which is to improve the prevention, diagnosis, and management of birth defects and deficits associated with congenital infections. Many knowledge gaps remain within the field of congenital Zika virus infection, as well as other congenital infections. With the end goal of improving functional developmental outcomes in children with congenital infections, tools need to be developed to identify children at high risk for developmental deficits earlier, maternal infection need to be prevented or treated, and infants need novel treatment options. Currently, there are no therapeutics for congenital Zika virus infection, diagnosis of congenital infection is fraught with limitations, and the pathophysiology underlying deficits is poorly understood. During the next 10 years, I envision my lab will focus on developing better tools for diagnosing congenital Zika virus infection, characterizing the brain changes that occur at a histopathological level for congenital Zika virus infection, and identification of viral and immune targets for therapeutics for congenital Zika virus and cytomegalovirus infection. Identification of humoral immune correlates of protection will provide targets for monoclonal antibody therapy development, which may provide pre- and post-exposure prophylaxis to limit fetal disease. All of these studies will lead to the earlier identification and accurate diagnosis of children with a high risk of developmental deficits as well as the identification and development of targeted therapies for congenital viral infections. These studies will continue to support the growth of trainees at all levels of learning in a laboratory environment that prioritizes feedback, support, and reproducible science. My laboratory will play a vital role in improving outcomes of children with congenital infections globally, working at the interface of translational animal models, molecular virology and fetal immunology.
I am dedicated to supporting students from all races, gender, social class, physical abilities, and sexual orientation. I believe that non-majority students face obstacles in successfully completing their program and navigating the network required to succeed in their training program. These unseen obstacles facing under-represented minorities need to be addressed at every level of our institution, and I have started to address this at the level of my laboratory and within my department.
Here is how I have worked to improve diversity, equity, and inclusion efforts to date:
1. I am dedicated to the training of future translational scientists, especially members of under-represented minorities. To support the training of under-represented minorities in science, I joined the University of Wisconsin Medical Scientist Training Program Summer Scholars as a research mentor for their inaugural summer in 2021. This program was designed for undergraduates who might not have access to research opportunities otherwise. I trained a female undergraduate student from a small liberal arts college last summer. I plan to continue being a research mentor to these Summer Scholars in subsequent years and looking forward to mentoring graduate students in the Neuroscience Training Program.
2. I am member of my department’s Anti-Racism Taskforce. This committee was developed within our department as a response to Black Lives Matter movement in the spring of 2020. As a member on this committee, I have been responsible for gathering data on the racial and ethnic background of employees within our department, and of physician trainees (i.e. pediatric residents) within our department. I worked closely with our human resources division and residency coordinator to collate this data and present it to the committee. I found that our department employee and residency backgrounds do not match the diversity seen in the state of Wisconsin. As a direct result of my presentation, our committee is now learning how the broader School of Medicine and Public Health tracks the racial and ethnic background of employees. My goal is to influence hiring, retention and professional development processes within my department to improve the equity and diversity of employees and trainees.
3. I lead discussions about diversity, equity, and inclusion within my laboratory group. By honestly discussing the challenges facing non-majority students, I hope to raise awareness within my team, and explicitly support minority students within my team. My team created a diversity statement during one of these discussions, which states that “Our lab values diversity: racial, cultural, religious, age, sex, gender, sexual orientation and disability.” We include this diversity statement on my lab webpage. I also incorporated a diversity statement in my graduate student mentoring philosophy which is shown on my lab webpage as well, “You must embrace diversity. We welcome diversity in the lab – racial, cultural, religious, age, sex, gender, sexual orientation and disability. Diversity in background and thought is the focal point of innovation, a crucial driver of scientific discovery.” I want my lab to be welcoming and supportive of non-majority students, and plan to have honest conversations about these challenges with all future graduate students.
Congenital viral infection, neurodevelopment, infectious diseases