Student Research Experience: Inborn Errors of Metabolism

I work as a Graduate Research Assistant at Children’s Hospital of Pittsburgh of UPMC, specifically assisting the Medical Genetics department’s ongoing clinical trials and other research projects in the area of inborn errors of metabolism. Working in this environment has helped elaborate on many facets of our program’s curriculum by showing that there are many ways to work meaningfully as a genetic counselor.

One study estimated that approximately 1 child in every 1,400
live births is diagnosed with an IEM.

Inborn errors of metabolism (IEM) is a name for a group of rare genetic diseases that affect the way a person’s body processes different substances, like proteins or sugars. While each type of IEM is generally quite rare, altogether these conditions are not infrequent diagnoses; one study carried out in British Columbia and published in 2000 (Applegarth et al) found a total incidence for IEM of 1 in every 1,400 live births. The severity and time of presentation for IEM can vary greatly between specific disorders, and even within one disorder. A disparity also exists for the availability and efficacy of treatment among IEM, which is why clinical trials and research are so important for the families touched by these conditions. Some conditions may be lethal in the neonatal period, while others are associated with little to no symptoms. Because metabolism is entwined with the food a person eats, some IEM, like phenylketonuria or phenylalanine hydroxylase deficiency (PKU), are considered to be very treatable with a protein-restricted diet. Even treatable IEM can bear the burden of strict lifestyle changes, financial costs, disease complications, and other sources of stress that affect a person’s quality of life.

Coordinating studies involves many parts that require lots of
thought, planning, and the occasional papercut.

My part in the important work done by Children’s Hospital is to support the study coordinators in the smooth facilitation of the studies. This can involve review of study subject medical records, data entry for different disease databases, creating recruitment letters for up-and-coming studies, calling subjects to clarify or receive more information regarding various outcomes, and yes, even the joy of filing all of the paperwork associated with the studies. While the latter has come with the odd papercut or two, the benefits I have received from the work has far outweighed this risk. As a genetic counseling student, this work has perhaps made me more familiar than the average student with the presentation, treatment options, and patient experiences in IEM, a vast and sometimes daunting disease category for learners such as myself. While every patient and family will have unique experiences, my work has allowed me to see some overarching themes in the sources of stress caregivers and patients can have. I feel this has been an irreplaceable part of my education, and I hope what I have learned has and will continue to have made an impact on the level of support I am able to provide to families.

While genetic counselors may take on several tasks that
are seemingly unrelated to patient care, their efforts make
a positive impact on patients' lives.

In an ever-changing environment for the field of genetic counseling, where many more genetic counselors are working in laboratories or in research positions, this student work has also given me a close-up view of the important roles these genetic counselors play. Before my time in this position, it was easy to imagine that these genetic counselors were several degrees removed from patient care. I now know that this is not the case. In addition to the nurses, dietitians, doctors, and other providers I have interfaced with as part of my work, the genetic counselors I have gotten to know through this work make such a difference in the care of the families in IEM with their unique understanding of the social and biological impact of these conditions. I consider myself indebted for the quality of their mentorship. This work has undoubtedly provided me with a stronger interest in research, a better understanding of the evolving genetic counseling field, and I think most importantly, a greater appreciation for the struggles and successes had by patients and families affected by IEM.

-- Jenni Peck, Class of 2018

Inside the Center for Craniofacial and Dental Genetics

The Center for Craniofacial and Dental Genetics (CCDG) is a unique, specialized research center located within The University of Pittsburgh's School of Dental Medicine. Collaborating with researchers from around the world, the CCDG team works to identify novel genes and environmental factors influencing craniofacial development and pathology.

Orofacial clefting (cleft lip and/or palate), one of the most common structural birth defects in humans, has a complex genetic etiology and is an active area of research for the center. Currently, our understanding of how and why orofacial clefts develop is far from complete, which often prevents precise clinical risk assessments for families affected by clefts. The CCDG team's work is making progress towards closing those knowledge gaps. The center also studies the epidemiology of dental caries (cavities) in rural Appalachia, with the hope of understanding the population's higher incidence of dental caries. Understanding the genetic factors pre-disposing individuals to the development of caries, and the interaction of those genes with the environment, can help to tease out causal factors and also, potentially, shed light on health disparities.

Aside from studying these conditions, another important research goal is to uncover genes which influence normal craniofacial development, and to explore the limits and variation of human facial features. Current and ongoing studies at the center involve the analysis of anthropomorphic measurements of the face and genome-wide association studies to explore associated genetic markers influencing the shape and size of facial structures: the eyes, nose, lips, brow, etc. Understanding normal facial development is a fundamental step in understanding pathways of associated pathologies.

As first year graduate student workers at the CCDG, we provide a variety of administrative support to the research team. Most simply, our duties include data entry and cleaning, pedigree verification and construction, and assistance with the maintenance of the center's massive amount of data and subject files (collected over decades!).

The data entry and file organization are certainly not the most glamorous part of a research project, taking part largely "behind the scenes", but like the work of a black-clad theatre set crew, our data entry efforts are essential to the research production. Along the way so far, we've learned much about the complexities of survey design, seeing questionnaire versions change and improve over the years as researchers figure out what works best, file systems, and spreadsheet/database construction for mass data analysis.

When we enter our second year and become more involved with the research itself (how exciting!), this experience of seeing the nitty gritty intricacies of such a large-scale research effort will remind us of the immense amount of leg-work done in order to build the rich data sets we have the opportunity to probe. The CCDG affords us an hourly job, a wonderful group of motivated researchers and co-workers, and valuable resources for our future thesis work.

In the following passage, we've each included a few words to describe our individual experiences and impressions working with the CCDG.

The first thing I noticed when I started working at CCDG was the welcoming atmosphere – from detailed directions on how to arrive for our first day to surprise treats in the breakroom. The staff did not hesitate to make Charlotte and me feel part of the team. I am looking forward to continuing to work at such a dynamic center and digging through more data for my thesis project!

-Alyssa

The staff and researchers at the center are fantastic, as Alyssa mentioned, they are always happy to lend a hand and check in about your day. It was also exciting how responsive the group was to our request for a meeting to talk about projects and our thesis work. Getting together with the researchers and brainstorming about the many ongoing and upcoming projects we can take part in was exciting and inspiring. 

-Charlotte