Dr. Sana Syed: From Family Inspiration to GI Innovation

By Dr. Sana Syed, Division of Gastroenterology, Hepatology & Nutrition

I am a Translational Clinical Scientist with a background in pediatrics, gastroenterology, global health/epidemiology, and data science. I also hold an adjunct faculty appointment at the Aga Khan University, in Karachi, Pakistan. My overarching research interest is to use machine learning to study big data in gastroenterology. In this context I study small intestinal structure and function in children with various small bowel enteropathies such celiac disease, inflammatory bowel disease here in the US and environmental enteropathy (global health) to drive innovations in possible treatment modalities.

My work over the last several years has centered around the use of machine learning/ artificial intelligence (AI) methods to study patterns of disease in small bowel biopsies. My work initially received seed funding from two UVA specific mechanisms (Engineering in Medicine, THRIV scholar) and recent career development funding from the NIH – NIDDK (K23 DK117061). I co-direct the Gut Intelligence Lab which is a multi-disciplinary team of medical professionals, data scientists and engineers geared towards exploring and solving questions related to gut structure and function. Our overall aim is to challenge and seek to shift clinical practice paradigms by utilizing novel Artificial Intelligence and Machine Learning based methods to innovatively contribute to the field of medicine – particularly pediatric gastroenterology.

Let me tell you a little about my background. When I think back and reflect, I realize that I come from an extremely motivated family. My mother lost her parents when she was very young – around 13 y – and was raised by her grandparents. This was during the time of the separation of Pakistan and Bangladesh. Her grandfather disappeared during the riots in 1971 so it was incredibly hard for my mother to pursue her dream of becoming a doctor. She eventually received her medical degree and, after having us three sisters, went to London for her post-graduate training in clinical pathology. This was when my younger sister was 6 months and I was 2 and my father, also a doctor, took care of us. Growing up hearing about my mother’s journey, we all knew it was immensely important for us to pursue higher education and be economically independent. I think back now that I have children of my own and realize how incredibly hard that time must have been for my parents. To see the life they lead now and the opportunities I have had – it was all possible because of their sacrifices.

My father’s story is no less inspiring! My father’s parents got married very young, as was the tradition in India at that time. At the time of their marriage, my grandmother could only read Arabic and had not received any formal education. My grandfather initially joined medical school, but was inspired by Gandhi and his socialist ideas to serve/ educate the poor and left medicine to become a teacher. Finances were tight – he would often take students on for free so my grandmother would work as a seamstress to help make ends meet. He eventually realized that he could support my grandmother to study and she could help increase the overall family income. What is amazing is the fact that she initially started with her ABCs after her first child was born! She then went on complete high school and eventually medical school, all while raising 8 children. The medical school she went to was in Sylhet in East Pakistan (now Bangladesh) while my grandfather’s school was in Karachi across the Indian sub-continent. This was an incredibly long distance in those times and they split the children between the two of them – all for the pursuit of education in the recognition that knowledge would transform their lives. When I was pursuing my clinical fellowship in pediatric gastroenterology, hepatology, and nutrition at Emory, Atlanta, my husband was in NYC so we did about 2 years of long distance. I remember telling my father how challenging life felt and he reminded of my grandparents and of his/ my mother’s time. It completely altered my perspective to think about their distance and the sacrifices they went through.

Eventually, my father and his seven siblings all became doctors – they actually married doctors and many of my cousins also went to medical school! I am the 30^th something doctor from my family, from OBGYNs, to pathologists, to microbiologists to anesthesiologists. Over the years, my family members have dedicated their careers to giving back to the community. So, from a very early age, I was very aware of  our privilege, of the access my sisters and I had to education at the best institutions and the opportunities open to us by virtue of how established our family was. It was instilled in us that it was imperative to give back. I grew up with a very strong sense of responsibility – I knew I had to somehow pay this privilege forward having seen firsthand how education can change lives. At every step of my education and career, I have reflected about what this privilege has meant for my life and my professional advancement.

In medical school, I realized I wanted to help effect change on a large scale and, for me, that was via research. My parents’ advice was to make sure I prioritized clinical training alongside my research, and, in retrospect, this was wise advice. I remember recently, Dr. Carlos  del Rio, Co-Director, Emory Center for AIDS Research, was speaking here at UVA and he shared how some of his most interesting grants were inspired by clinical challenges he had faced while seeing patients.

Next, I needed to figure out what clinical work was right for me. I decided on pediatrics because we had inspiring leaders in pediatrics that came out of the Department of Pediatrics from my medical school, the Aga Khan University in Pakistan. From an impact standpoint, I knew that about 1/4^th of the world’s population consists of children. As a medical student, I decided that if I could spend my professional career focusing on creating positive change in the health of children, hopefully my work would  have a significant impact.

After medical school, I took two years to focus on what I now realize was essentially a large data science project. I joined the Department of Pediatrics as a research assistant for the 2010 Global Burden of Disease Study (GBD – a WHO/Gates initiative), where I worked with the Infections Morbidity/Disability Group under Dr. Anita Zaidi. My role in this international team of scientists and policy makers involved systematic literature review, data entry, and analysis. Combined with my early childhood experiences, this work cemented my desire to pursue clinical research as a means to bridge the gap between scientific knowledge and implementation. As part of this work, I traveled to the London School of Tropical Health and Hygiene for a stakeholder meeting and got to see people in action – physician researchers who were doing clinical work, research, AND speaking to policy makers to bring about change. This was immensely inspiring and I met many people who, at that critical juncture, I saw as role models for what I would do in the future.

During my pediatrics residency at Duke, I had many different interests including Hem-onc and PICU/NICU. I decided on Pediatric GI, again using a data driven approach. The GBD project along with others had shown nutrition to be an underlying attributable cause of all cause mortality in children under the age of 5y. I thought, “let me invest in really understanding gastrointestinal disease and nutrition.” This decision took me to Atlanta, where I did a three-year fellowship at Emory in Pediatric GI. For my research years, I pursued a Master’s in Clinical Research via their CTSA and for my capstone, I worked on a database project looking at iron deficiency in the US, Colombia and Mexico with a secondary project focusing on iron deficiency biomarkers in children with Crohn’s disease.

From there, I wanted to pursue a career as a clinical scientist with focus on both global health along with work here in the US. I spent a year at Boston Children’s/ Harvard Medical School as a fellow studying clinical nutrition. At the same time, Sean Moore, now my mentor here at UVA, had been pursuing a similar career track studying malnutrition and I reached out to him. My mentor in Pakistan, Anita Zaidi, was now a Director at the Gates Foundation and she introduced me to Sean. He had just gotten funded by the Gates Foundation for studying environmental enteropathy in Pakistan using celiac disease here in the US as a comparative enteropathy. He was then recruited to UVA from Cincinnati Children’s – and that in a nutshell is how I came to UVA! I wanted to work on this Gates project and have Sean Moore mentor me to successfully develop a career as a clinical scientist.

There are so many aspects to the story – one part to highlight is that of networks. Sean’s mentor at Cincinnati Children’s Ted Denson, and my mentor, Subra Kugathasan at Emory, were close collaborators working together on a pediatric IBD project in the US gathering human tissue to collect ‘omic data. Sean with Asad Ali, a co-PI in Pakistan, proposed this ‘big data ‘omics’ approach in a global health setting, which was really revolutionary. In some ways, the work we are doing now all came down to thoughtful networking, timely luck, and appreciating the big picture of how everything fit together.

At UVA, I was lucky to get immense support both from our Chair, Dr. Nataro and Sean Moore, which gave me time and space to really think deeply about what my career should look like and what direction to take my research. I wanted to push the boundaries beyond what my family had done. I have always been a believer in “reading the wind” and that, incidentally, is also what Sean encouraged me to do.  When I first came to UVA, the winds were saying “data science” with large institutional investments in a School of Data Science among other things. Sean’s perspective was that the true bottleneck in medical high dimensional data was understanding biology while undertaking meaningful analysis. As a physician, investing in data science training would allow me to create a unique translational niche.

As I was working on my NIH K award aims, I remember Jim sent me a link from a nature paper on the use of AI image analysis to detect skin cancer (https://www.nature.com/articles/nature21056) and I thought, “I am not sure if I can do this! This is really complicated” but I decided to put my ideas together. I submitted my grant initially to the Gates Foundation with the idea to use AI to study patterns in human tissue. I did not get the grant and I was really frustrated. I went home and googled “engineering and medical grants”. There was an Engineering in Medicine mechanism at UVA that fit that – and the grant deadline was THAT DAY. I submitted and I got it! This initial grant was about $70k. Everything has continued to grow from there with subsequent funding from THRIV here at UVA and then NIDDK.

Here is what I am working on now. Anytime I see a patient in GI clinic, I have to decide which patients merit a look from inside for us to sample tissue to study disease via an endoscope. This tissue is typically archived for research. We have been mining this tissue and studying it for patterns that map on to clinical phenotypes. An easy way to think about this is to consider Facebook. When you upload a picture on Facebook, there is auto tagging – how does that happen? Facebook uses deep learning algorithms to study all the pictures you have tagged along with billions of other photos on Facebook as a ‘training’ dataset. It picks out patterns across the group and tags based on these patterns of previous data. When you upload a new untagged image, it autotags your image using this new image as a ‘validation’ dataset.

For biopsies, we know clinically that patients with specific phenotypes group together. We are looking across multiple biopsies across phenotypes in diseases, such as Celiac and Crohn’s disease, and looking for distinguishing microscopic defining features. The next step is to go back and study gene expression in specific biopsies.

Let me give you an example: I recently saw a 22-month-old patient in clinic. The child had diarrhea and was not growing. I suspected Celiac disease and confirmed this with blood work. I went over how removing gluten from the diet is the first step and explained the possible risks moving forward – specifically that 10-30% of patients with Celiac disease might develop diabetes later in life. The mother said, “Is there no way for you to tell me about MY child’s risk? Is our risk 10% or 30% or lower?”

We do not have the ability to give this personalized level of disease prediction right now. But intuitively, we know that two patients with the same disease, such as Celiac disease or Crohn’s disease, have very different personalized experiences of their disease course.  The goal is to use machine learning and the powerful computing resources available to us to put together a personalized profile for each patient and that is immensely exciting.

When I travel to our study sites to villages in rural Sindh, Pakistan and see incredibly malnourished children with poor access to health care facilities, it makes me angry. I feel the same anger and impetus to DO something when I see patients in the US with whom we are limited by what FDA approved therapeutic treatment options we currently have available to us. When I do not have a better answer to give – for example to that mother of my 2-year-old patient with celiac disease, or when I do not have a better, more personalized biologic infusion to offer a patient with Crohn’s disease – it pushes me to ask the question, “what can we do to serve our patients better?” My clinical interactions drive me to find a way to give back to the patients that I see. As physicians, we are privy to very private, personal stories from our patients who share these in the hope that we can solve their problems, and for me, research is how I invest in creating future change and opportunities.

People often ask me, “How do you do so much? How do you find the time?” My answer is always that you have to find time for the things that are important and meaningful to you, once you figure out what those are! For me, my family and my work are the two most important priorities. Professionally, I have a very strong sense of what I have to accomplish because of the immense educational opportunities I have had both growing up and here in the US throughout my clinical training. I feel an immense sense of responsibility and the reason I keep pushing so hard is this sense of urgency to give back.

I was once told “find what you love and you will never work a day in your life” – I can completely say I have the immense privilege and luck to have found what I love. Every day I come to work and it does not feel like work when I have so much fun doing what I do! This is because of the amazing colleagues and mentors I have here at UVA and the team I work with. The Department of Pediatrics at UVA is an amazing place to work at and I am so excited to be able to contribute to advancing research, clinical care, and education as faculty here!

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