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   

Genetic Counseling Assistant Experience at Children's Hospital of Pittsburgh

A picture of Children's Hospital of Pittsburgh.

I currently work as a Genetic Counselor Assistant (GCA) in the Medical Genetics Department at Children’s Hospital of Pittsburgh of UPMC. I was hired in July, and having the opportunity to work part-time at Children’s while attending Pitt is a dream come true. I have always loved working with children, and directly helping the genetic counselors with their various day-to-day tasks gives me insight into the many roles and responsibilities of pediatric genetic counselors. As a GCA, some responsibilities I have include writing letters of medical necessity, contacting insurance companies regarding genetic testing, filling out test requisitions, and doing some preliminary prep work for patients who will be seen in the next week. Recently, I have started calling new patients to give them about a genetic counseling appointment, to ensure they know what to expect when they arrive at the hospital.

One thing that is exciting to see as both a genetic counseling student and a GCA is the rapid growth in the field. In addition to hiring me as a part-time GCA this summer, Children’s hired two other GCAs with whom I have the privilege of working. Also, four genetic counselors have been hired since I started my position (doubling the number of genetic counselors in the Medical Genetics Department!), and there is still a need for more. As an emerging professional in this field, having the chance to work with genetic counselors with wide ranges of experience, from recent graduates to experienced genetic counselors, has been an incredible learning opportunity.

Working as a GCA allows students to integrate
class and clinical knowledge while getting paid.

Although balancing work and school can sometimes be difficult, most of the time the material I learn in class and my work position go hand-in-hand. I am fortunate to have days where I work in the morning and then attend class in the afternoon, where we discuss symptomology, conditions, or genetic testing that I had just seen in my work setting. Being a GCA in a pediatric setting facilitates this learning process, due to the wide range of disorders and genetic variants that children may have who are referred to Medical Genetics. In a similar fashion, being a GCA also allows me to synthesize material I learn in class and gives me the opportunity to apply it in a clinical setting. I expect that my work position will also ease my transition from graduate student to genetic counselor, since I will have had almost two years of experience doing many of the daily tasks that are expected of genetic counselors. Just after a few months, I have grown comfortable using the electronic medical record systems, working with other medical professionals, and calling patients and families. My experience thus far has begun to equip me with core skills of genetic counselors, including knowledge and interpersonal communication, which will be invaluable to my future career.

While I have learned a great deal about genetic counseling as a GCA, I would have to say a highlight of my job is the entire Medical Genetics Department staff. My supervisor fosters a supportive, open environment, and I feel everyone at the office is a work family. Everyone has a strong work ethic, and the genetic counselors are incredibly kind and generous with their knowledge. Yet, there is still fun on a daily basis, as well as an ample supply of office treats! Recently, the department has begun organizing monthly social events, including escape rooms and haunted houses, to promote staff bonding and friendship outside of the office. The compassion and camaraderie among the counselors, new and experienced, really makes me excited to come to work every day. I am grateful for the professional opportunity to be a GCA at Children’s, and I look forward to learning more and continuing to hone my skills as a graduate student and future genetic counselor.

-- Rebecca Clark, Class of 2019

Dealing in the Rare: Cutis Laxa

In genetics, we often say that we deal in rare. This is especially true in my work position in Dr. Zsolt Urban’s laboratory in the Department of Human Genetics. I have the unique opportunity to work alongside Dr. Urban and the other hardworking members of the lab as a clinical study coordinator. The Urban lab studies a rare connective tissue disorder called cutis laxa, a condition characterized by loose, lax skin that can also affect many different body systems. The effects of cutis laxa on the body are widespread because it causes changes in the extracellular matrix, a structural component of the connective tissue. Connective tissue is found throughout the entire body and can be thought of as the glue that holds our bodies together.

 

A representation of the extracellular matrix.

Over time, pathogenic variants in over ten genes have been found to disrupt the extracellular matrix and cause cutis laxa. While changes in these different genes can cause a similar condition, pathogenic variants in the different genes can present with unique clinical features, warranting the delineation of cutis laxa into gene-based subtypes. Our study participants are truly the driving force behind our growing knowledge of the similarities and differences among the different subtypes of cutis laxa . As the study coordinator, contacting our participants, consenting them to our study, and gathering their clinical information is an essential part of my job. This is an important step in establishing a natural history of the different types of cutis laxa. By providing clinical information, participants from all over the world are contributing to our insight on the clinical course of cutis laxa. This information is invaluable to individuals and families faced with a rare disease diagnosis who every day deal with the unknown. This information also helps direct future research and hopefully better diagnostic tools and treatments.

Taking family histories and coordinating sample collection for genetic studies from our participants are other important aspects of my position. While molecular analysis determines the subtype of cutis laxa within an individual or family, when it is combined with detailed family histories, it allows us to determine the inheritance pattern of cutis laxa in families. Autosomal dominant, autosomal recessive, and X-linked forms of inheritance have all been observed in families with cutis laxa. Knowing how cutis laxa is inherited within a specific family allows us to determine at-risk family members for testing as well as recurrence risk for couples.

The Rare Disease Day logo.

This position exemplifies the merits of rare disease research, an area that has fortunately been able to grow rapidly with advances in genetic knowledge and technology, as well as through the support of institutions like the National Organization for Rare Disorders (NORD)* and the National Institute of Health, which has programs like The Genetic and Rare Diseases Information Center (GARD). This position has also allowed me to glimpse into the lives of families facing the challenges of rare disease every day. The opportunity to witness their strength, resilience, hope, and grace has been the greatest privilege of this position. Our study participants have taken on tremendous advocacy roles throughout their lifetimes and are truly inspirational.

-- Emily Spoth, Class of 2018

*NORD was originally formed as a coalition of parents of children with rare conditions and has grown to include over 250 patient organization members. One of these members is Cutis Laxa Internationale, centered around cutis laxa! Every year, NORD sponsors Rare Disease Day. The next Rare Disease Day is February 28, 2018! You can learn more at their website: www.rarediseaseday.org

Student Work Positions: TRiNDS Clinical Research Assistant

For my student work position, I have the pleasure of working for TRiNDS, a full-service CRO specializing in neuromuscular disorders (DMD, BMD, FSHD, etc) that also runs the coordinating center for the CINRG network. Confused by the alphabet soup? Don’t worry, I was too when I first started. I learned very quickly that the clinical research world  is full of acronyms. Let me break them down for you.

TRiNDS stands for Therapeutic Research in Neuromuscular Disorders Solutions. TRiNDS is a contract research organization (a CRO), a type of company that can support pharmaceutical or academic centers for their clinical research needs. TRiNDS does not directly conduct the clinical research, but helps support the clinical operations, data collection and management, and analyses of research studies. TRiNDS is a unique CRO in that it specializes in neuromuscular disorders, including (but not limited to) Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD) and Facioscapulohumeral Muscular Dystrophy (FSHD). These are rare, debilitating diseases that cause progressive loss of muscle function and mobility starting in early childhood. Several individuals at TRiNDS have worked with the Cooperative International Neuromuscular Research Group, or CINRG for short. CINRG is a network of professionals and institutions around the world that have partnered together to study these rare neuromuscular disorders. Through inter-clinic and international collaboration, CINRG aims to improve the quality of life for individuals and families dealing with neuromuscular disorders through clinical research investigations. TRiNDS grew out of the CINRG coordinating center (CC), and now continues to coordinate the network activity.  So, to sum it all up, TRiNDS is a CRO specializing in disorders like DMD, BMD, FSHD, etc that also runs the CC for the CINRG network.

As the TRiNDS Clinical Research Assistant, I help with the day-to-day and clerical activities at TRiNDS. Some of my responsibilities include managing company files, scheduling meetings, and coordinating supplies and equipment needed by the CINRG sites to collect strength and function assessments. I also help draft company documents, and I was involved in the development of both the TRiNDS website and the recently-updated CINRG website. These activities have allowed me to peek inside the world of clinical research trials and learn about the ins and outs of developing therapeutics for rare disorders. I have gained an appreciation for how much time and effort goes into completing a successful clinical trial, and for the dedicated professionals and brave families who devote their lives to furthering knowledge about these disorders. While TRiNDS specializes in many neuromuscular disorders, I have mostly been exposed to trials related to DMD, which has given me an insight into the amazing Duchenne community. I am in awe of the courage and optimism of the DMD community, and the more I learn about DMD, the more inspired I am to get involved and to work to my fullest potential. I am excited knowing that I will be able to devote my graduate thesis project to furthering knowledge about DMD.

I also work with a wonderful and diverse team at TRiNDS, and it has been a joy to collaborate with and learn from my growing group of coworkers. Two TRiNDS employees are actually genetic counselors, so it has been very eye-opening to see how their careers have progressed so far and how they use their skills as genetic counselors in the world of clinical research. Going into graduate school, I knew that I wanted exposure to as many different genetic counseling roles as possible, so I feel incredibly lucky to have the opportunity to learn from these genetic counselors working in unique positions.

Working for TRiNDS is shaping my professional identity and helping me grow into the genetic counselor that I want to be. No matter where I end up after I graduate, I will continue to utilize the knowledge and lessons learned through this position, which I know is setting me up for my best future. To say I am grateful for this experience is an understatement, and I am looking forward to seeing how the company grows as I continue to work through my second year.

-Julia Stone, Class of 2017

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