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Nature Communications co-author Dr. Casey Dorr speaks about pharmacogenomics in Indigenous communities

Presenting seminar “Pharmacogenomics and Spatial omics in Kidney Transplantation” at the University of Minnesota Duluth School of Medicine Seminar Series, Duluth, MN Feb 7, 2024.

After nearly three years of collaboration and enduring five rounds of peer review from the first submission, Casey Dorr, PhD, a nephrology investigator and descendant of the Mille Lacs Band of Ojibwe,  has achieved a monumental milestone. His name now graces a coveted co-author credit in the prestigious scholarly journal, Nature Communications. This achievement, a testament to his perseverance and dedication, resulted from a fruitful collaboration with fellow pharmacogenomics researchers, Dr. Katrina Claw at the University of Colorado and Dr. Erica Wooddahl at the University of Montana. Their collaborative article, “Implementing community-engaged pharmacogenomics in Indigenous communities,” stands as a beacon of their collective efforts and the transformative power of collaboration in scientific research.

Dr. Casey Dorr

Dr. Dorr is a nephrology investigator at Hennepin Healthcare Research Institute (HHRI) and Assistant Professor at the University of Minnesota’s Department of Medicine in the Division of Nephrology and Hypertension as well as the Department of Experimental and Clinical Pharmacology in the College of Pharmacy. He is also the Co-Director of the Pathways to Research Program (PReP) and Advanced Pathways to Research Program (A-PReP).

Although Dr. Dorr investigates mechanisms of kidney diseases, his research also centers on pharmacogenomics, a field with immense promise in improving health outcomes such as transplant and kidney diseases. This branch of study, informally known as PGx by researchers, delves into the efficacy of medications dependent on genetic variations. The potential of pharmacogenomics to enhance health outcomes, particularly in underserved populations like Indigenous communities is a light of hope. Inclusive precision medicine, a product of this knowledge has the potential to reduce health disparities and elevate overall health outcomes.

Pharmacogenomics, in simpler terms, is “how genetic variation is related to medication response. Say you take a drug, and maybe it wears off in four hours. Someone else, you know, may take the same drug and it lasts for like eight hours; this has to do with how fast your body clears that drug out of the system and your genetics affect that, how fast you clear the drugs. So that’s what pharmacogenomics is, how your genetics affect response to drugs,” said Dr. Dorr.

His educational background includes a Bachelor of Science in Cell Biology, Chemistry and American Indian Studies at the University of Minnesota (U of M) Duluth. He later completed his PhD at the U of M, Twin Cities, in Molecular, Cellular, Developmental Biology, and Genetics. Following his PhD, Dr. Dorr completed two post-doctoral fellowships, the first at the U of M’s Masonic Cancer Center in Cancer Genetics and the second at his future workplace, HHRI, in Nephrology and Molecular Epidemiology. A dedicated learner, Dr. Dorr completed a Master of Science in Bioinformatics and Computational biology in August 2023 from the University of Minnesota.

The perfect dose

Ever since the COVID-19 pandemic, you can’t escape the conversation around mental health. PGx is no different. It’s become a hot topic to research because mental health drugs are well-known for having a genetic component. To maximize their efficacy, you have to get dosages just right.

The problem with getting dosages just right? Most drugs were developed and tested on white men. Dorr and his team are trying to remedy this problem by diversifying the applicant pool in drug study trials to ensure that “people get the right drug at the right dose for the right person.” Digging even deeper, Dorr’s team is also inspecting the differences within intraracial populations.

“But just within African American people, there’s a big change and variance in how people respond to different drugs. It’s not just based on what race people are. There are genetic components within populations, within ethnicities that may affect how you respond to a drug. So, I also wouldn’t say just give someone a drug based on their race or ethnicity. That’s not a very good approach either.”

Nature Communications infographic highlighting the key areas that need improvement for better health outcomes in American Indians and Alaska Natives communities.

“We highlight key areas in pharmacogenomics (PGx) research and clinical implementation to bring about better health and well-being in AIAN communities: (1) Engaging the community (center), (2) increasing PGx knowledge of AIAN variation, (3) clinical implementation of PGx, and (4) inclusion of traditional knowledge and practices. Engaging the community is at the core, and this includes coordinating research with the tribal community, obtaining tribal approval, and encouraging tribal members to participate in data analysis, interpretation, and writing of results. Increasing knowledge related to PGx variants by including Indigenous peoples in basic and clinical research and the workforce, support for clinical implementation into healthcare, and including traditional knowledge and practices need to increase.”

The genetic approach, though, is, so if we know if they’re a fast metabolizer of a drug or a slow metabolizer of a drug; if you’re a slow metabolizer of a drug, it’s going to build up in your system. It’s not going to get cleared out much. And so, a small dose may be more, maybe too much, whereas as a fast metabolizer is going to clear the drug fast. They’re going to need higher doses to get that effect.”

To get more Native people into drug study trials, you must get the tribes involved. According to Dr. Dorr, globally, there are over 500+ tribes, each with their own laws, political and government structure. Researchers would need buy in from each individual tribe by persuading them to see the benefits. To further complicate things, some tribes, like the Navajo Nation, even have a moratorium on genetic research.

Networking is key

Networking, a crucial aspect of professional growth, was pivotal in Dr. Dorr’s journey. After publishing a previous article on ethics within the research of Indigenous people in Nature Communications, Dr. Claw was approached to form a team and write an abstract for a special issue on biodiversity in human research. Dr. Wooddahl and Dr. Dorr, seasoned researchers in Indigenous pharmacogenomics, came into the picture through networking in a professional organization called the Society for the Advancement of Chicanos and Native Americans in Science (SACNAS). This instance highlights the importance of networking in creating new opportunities and collaborations.

Six months and one short abstract later, the team was approached by Nature Communications to dive deeper into the topic in a full-length, peer-reviewed article. Dr. Dorr looked at this opportunity as his duty to give back. “And it’s important [,] I was raised to give back to our community, to give back to Ojibwe people. It’s how my father, and my grandfather and aunts and uncles raised me. So, it’s important to me to do what I can to give back to Native people.”

Through another networking connection, this time through the American Indian Science and Engineering Society (AISES), he synced up with former National Institute of Health (NIH) employee and Dine (Navajo people) tribe member David Wilson. Its through this connection that Dr. Claw, Dr. Wooddahl, and Dr. Dorr were able to interview several employees in the bioethics department at the NIH to obtain more statistics. The stats that helped to contribute to Figure 1 are seen above.

The path to acceptance

While Dr. Dorr does have 20+ publications under his belt, every publication’s acceptance criterion differs. Some journal articles are accepted on the first try, some take a month or two, and then some get rejected a handful of times and Dr. Dorr is still trying to figure out how to publish some of his work.

In this paper, the researchers each wrote designated sections, and there were many peer review edits, but Dr. Dorr is fearless of the red pen because researchers and scientists deal with constant rejection. “That is a mindset I had to develop a long time ago; I think I have over 20 publications nowadays, but every draft, I want those red marks. That means the person invested time and energy into that article, and they care about you. They care about your best product.”

Advice for early career researchers and scholarly writers

Dr. Dorr shares a valuable piece of wisdom for all researchers, especially those in the early stages of their careers. He emphasizes the need to cultivate resilience in the face of rejection, a shared experience in the scientific community. “It’s letting that roll off your back and you learn from why did something get rejected? What can I learn from that? How can I improve? Now I’m going to try again. It’s that resilience that is so important in science and research and clinical work.

Clinical research, that’s something. I run these summer programs for students at the U of M. That’s something we really try to teach the students early in their careers. The point is you’re going to get rejected. Don’t let that define you. Don’t let that stop you from accomplishing your goals and your dreams. Learn from it. Try again. And I’ve been doing that my whole career, and that’s just something we need to succeed, is how to handle rejection, so that you can turn that into success” he advises.

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