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   

Investigating the Etiology of Treatment-Refractory Depression

Treatment-refractory depression is depression that has not
responded to at least two courses of antidepressants.

In addition to my classwork and rotations, I work as a research assistant with Dr. Lisa Pan in the Department of Psychiatry. Dr. Pan’s research has investigated the etiology of treatment-refractory depression – depression that has not responded to at least two courses of antidepressants. A number

of individuals with treatment-refractory depression have significant family histories of mental health issues. Some of Dr. Pan’s recent work has evaluated patients’ cerebrospinal fluid for molecules involved in the metabolism of neurotransmitters. Discovery of deficiencies in patients has allowed for supplementation of missing metabolites, which has been remarkably successful in improving their depression symptoms. Researchers associated with the study are now performing genetic analyses to determine whether genetic variations are associated with patients’ symptoms. My work with Dr. Pan involves documenting patient pedigrees, investigating genetic analysis findings, writing a case study, and preparing to deliver results to a patient.

Working in research has reinforced how quickly things evolve in genetics. New findings occur every day, and treatments are developed to improve the health of patients. Seeing this aspect of genetics gives me a new appreciation of how the information and treatments we provide patients in clinic were developed. Accepted treatments were once experimental approaches. As additional knowledge about the genetics underlying psychiatric diseases emerges, new therapeutic approaches may emerge.

Connecting genetic factors to treatment-refractory depression
and other psychiatric disorders may help scientists find new
treatments for these illnesses by unlocking another piece of
the puzzle.

Genetic counseling related to psychiatric disorders is a new and growing field. Since psychiatric disorders, such as depression, bipolar disorder, schizophrenia, and autism, are complex, strong genetic associations have been difficult to identify; however, significant strides have been made in determining genetic and environmental contributions to mental health. Family history of psychiatric disorders can increase the likelihood of an individual developing a mental health condition. Certain genes have been found to be associated with some psychiatric disorders. With knowledge about psychiatric disorders and genetics increasing rapidly, development of guidelines about genetic counseling in relation to mental health is important. At the 2017 NSGC conference, I had the opportunity to join a meeting of the Psychiatric Special Interest Group, with other genetic counselors interested in advancing the field of psychiatric genetic counseling. We discussed ways to address family and personal histories of mental illness that come up during genetic counseling sessions as well as specialized clinics for psychiatric genetic counseling.

Being able to work with research finding new connections between depression and genetics and seeing these connections directly applied to help patients find relief has given me insight into current and future needs in the genetic counseling field, and I hope to use this perspective and knowledge to help my future patients!

-- Kaitlin Sullivan

Interview Advice from the class of 2019

Congratulations on having an interview! My advice to you is to be yourself, have questions, and also interview the school. Remember, you already proved yourself on paper, now programs want to know your personality and style to see if you’d be a good fit for the program. You will have plenty of opportunity to ask questions, so be sure to have them prepared for your interviewers, faculty, and students. Finally, ask yourself if you could see yourself at this program – do you like the city, the school, the students, the rotations, the class set-up,  extracurriculars, etc? Good luck!

-Megan Hoenig

Congratulations on your interview! Amongst all the excitement and jitters you’re probably feeling, don’t forget to take a deep breath and be yourself! Take advantage of different opportunities to interact with faculty and current students. These moments will be a great chance to ask more questions and get to know the dynamic of the program to see if it’s the right fit for you. Good luck!

-Alyssa Azevedo

Take a second to pat yourself on the back, you got an interview!!! Now the hardest part is out of the way, and they already think you’re pretty great, so now is the time for you to figure out if it’s the place for you.  I recommend coming up with a list of questions and taking notes after each interview so it is easier for you to look back on. I had friends (even those outside of science) who helped me practice for interviews. I found being forced to say some of my answers out loud was very helpful, and I found my best interviews were after I’d had a chance to practice.  Wear something that makes you feel great about yourself!

Good luck!

-Natasha Robin Berman

Congratulations! Take pride in the fact that you got an interview because it is quite an accomplishment. Remember that you are interviewing Pitt as much as they are interviewing you. Explore the area if you get the opportunity, and talk to as many students and faculty as possible. Just stay calm because everyone is genuine and wants to get to know you! Good luck!

-Rebecca Clark

Congratulations on getting an interview, you are one step closer to becoming a future genetic counselor!  My advice would be to write down questions beforehand, it is so easy to forget questions in the moment.  This will also allow you to go back and look at what you asked and what some of the answers to those questions were.  Also, don’t be afraid to interact with the faculty and current students—remember these could be your future classmates, professors, and colleagues.  Lastly, (try to) relax and be yourself!  Best of luck!

-Rachel Sutton

How exciting! We look forward to welcoming you during your interview. Interviewing is great, because it is one of a few times in life that you get to really show off how impressive you are in person, with a confidence-inspiring backdrop of how impressive you already looked on paper! My advice is to take some quality time to explore and understand your unique priorities and motivations, personally, professionally, and academically. If you have done this before your interviews, it is much easier to come up with critically important questions to ask about what life is like as a student in the program; specific questions that can really help you find out if it is a good fit for you. In my interview experience, I found that each program had unique vibes, strengths, and focuses- make sure you explore and feel these aspects out, then write them down so you remember how you felt about the people, school, and area/city. Cheers!

-Charlotte Skinner

Woo! Way to go- you’re halfway there! I cannot really say more than any of my classmates above have so beautifully articulated. Just be yourself, do your best, and really try to have fun! Wherever you choose, you’ll be spending the next 2 years there so try your best to get a sense of not only the school and faculty but the city as well. Take lots of notes right after your interview, what you thought of everything you heard and saw that day- it will really help you when it’s ranking time. I wish you all the best of luck, I’m sure you’ll do great!

-Samantha Afonso

Congrats! You've done the hard work. Now, give yourself the best chance to show everyone how amazing of a classmate and future colleague you will be! Don’t underestimate the importance of the little things: Make sure you feel comfortable in your clothes (heels and snow were a no go for this Californian), have eaten something and gotten plenty of sleep, and maybe listen to a few good pump-up tunes. Give yourself plenty of time to find the interview, too. Campuses can be confusing, and buses delayed. These all may sound minor, but they’ll help keep your mind (relatively) relaxed and focused on the important parts of the day. The weeks before, I also practiced saying out loud why this is a career I feel so passionate pursuing. It was all there in my head, but verbalizing it the first few times was definitely a bit awkward. Have fun!

-Caitlin Russell

Congratulations!  You’ve worked very hard and now you’re one step closer to your goal.  My advice is to take a deep breath and try to relax.  Everyone is warm, welcoming and kind, so it’s not hard to feel at ease with them.  Smile, ask questions, and remember that this is your opportunity to talk about all of the amazing things you’ve done so far, especially the things that may not have fit well on your résumé!

-Meghan Cunningham

You are clearly impressive enough to secure an interview, so the next step is seeing if you and the program are a good fit.  On paper, you’ve met the requirements, so now is the time to stop stressing about that low(er) organic chemistry grade and really focus on why you want to be a genetic counselor and how that aligns with the program’s values.  Being able to communicate your unique motivation for pursuing a master’s in genetic counseling is vital to any interview. Being able to speak to how your personal and career goals align with the vision of the program will set you apart from other applicants.  UPitt stresses the importance of making sure the program is a fit for you-- this is not a line.  All programs are demanding in their own way and asking questions to ensure that you can commit to their standards will save you from choosing an experience that won’t serve you or the program.  In the same vein, answer questions honestly.  Just like any other interview, giving an answer you think you are expected to give will often come across as disingenuous.  (Remember these are counselors who can pick up those subtle cues!)  Maybe less obvious, but enjoy getting to know the other applicants.  You may see them at other interviews; and I know that several women in our class actually forged friendships during the whole interview process.  If nothing else it can help calm the nerves seeing that other people are in the same boat as you!

-Kelsey Bohnert

It is important to make sure that you are not only prepared for your interview, but also that you are prepared to get your own questions answered and investigate the campus and city!  Knowing your strengths and weaknesses, being prepared for case simulation questions, and being able to explain how you know you want to be a genetic counselor are all important components of arriving prepared.  I would also suggest that you look into opportunities specific to the University of Pittsburgh so that you can ask for more details when speaking with faculty and students.  This both gives you a better understanding of the program and shows your interest to those with whom you speak.  Explore the city if you have the time--it will help you envision being here.  Definitely try to enjoy the experience!

-Sarah Brunker

Class of 2019