Shami Kanekar, PhD, is a neuroscientist and a Research Assistant Professor in the Department of Psychiatry. Her groundbreaking research is in the areas of depression, anxiety, and substance use.
HMHI Research Spotlight: Shami Kanekar, PhD
Shami Kanekar, PhD, is a neuroscientist and a Research Assistant Professor in the Department of Psychiatry at the University of Utah School of Medicine. Her research in the areas of depression, anxiety, and substance use, has been groundbreaking.
We asked Dr. Kanekar a few questions about her research, her work at Huntsman Mental Health Institute (HMHI), and what she enjoys doing when she is not working.
What is your area/areas of specialty?
I am a neuroscientist by training. The focus of my research is the impact of hypobaric hypoxia (as experienced at moderate altitude) on brain physiology and mental health. I was instrumental in establishing a novel animal model to study altitude-related depression, based on the finding that rates of major depressive disorder (MDD) and suicide increase worldwide with altitude of residence. With this model, we have determined that living at moderate altitude can be an environmental risk factor for vulnerability to mental health disorders, including MDD, anxiety disorders and methamphetamine misuse. We were the first group to identify moderate hypoxia as a physiological risk factor for mental health disorders. We find that rat brain physiology and behavior change with housing at altitude in a sexually dimorphic pattern, with females more vulnerable. We also determined that most SSRIs are ineffective in both sexes at altitude. Since SSRIs are the primary antidepressants/anxiolytics currently prescribed, MDD and anxiety disorders may be more treatment-resistant at altitude. My group also identified bioenergetic compounds as effective antidepressants for SSRI-resistant depression at altitude. In addition to my preclinical studies, I initiated collaborative projects with the Utah Lung Health Group to study depression in lung disease patients (who experience chronic hypoxia through lung dysfunction) and to identify systemic biomarkers of hypoxia and MDD in these patients. I also initiated a demographic study on opioid use at altitude: we found that prescription opioid misuse increased with altitude of residence in women, while overdose deaths by prescription opioid misuse increased with altitude in both sexes. Living at altitude was previously documented to be detrimental to misuse of stimulants (cocaine, methamphetamine). This study was critical in showing that living at altitude is also detrimental to the misuse of sedatives (opioids) and may be especially damaging to women.
"I love the translational aspects of my work, and the potential of helping patients in need. I enjoy the creative aspect of conceptualizing and designing experiments. I enjoy writing and reviewing manuscripts. And as gut-wrenching as writing grants is, I still enjoy the laying out of ideas and describing how we will address the big questions."
What do you love most about the work that you do?
I love the translational aspects of my work, and the potential of helping patients in need. I enjoy the creative aspect of conceptualizing and designing experiments and coming up with new research areas to explore. I enjoy writing and reviewing manuscripts. And as gut-wrenching as writing grants is, I still enjoy the laying out of ideas and describing how we will address the big questions. I have been lucky in being able to work with outstanding lab personnel, colleagues and mentors. I enjoy collaborating on research projects with other PIs. I have particularly enjoyed working with scientists who joined my lab as technicians or post-doctoral interns, bouncing ideas off each other and getting some exceptional work done. Over the years, we have also had several high school and undergraduate students do summer internships in our lab and it’s been rewarding to mentor them and help them on their way to graduate or medical school.
What is the latest update(s) on your research?
Last year, I received a grant from the Margolis Foundation for the purpose of identifying systemic and brain biomarkers for depression at altitude. Using these funds, we have found that housing at altitude can induce systemic inflammation, as seen in elevated serum levels of the inflammatory cytokine interleukin 6. This is important in showing a link between our rodent model and human disease: elevated systemic levels of interleukin 6 is a marker linked to both MDD and suicide. Studies are in progress to characterize other biomarkers for depression at altitude, including transcription factors activated by hypoxia, altered expression of neuroprotective factors and stress axis markers. MDD is often comorbid with anxiety, and our recent studies find that rats of both sexes exhibit symptoms of anxiety at altitude, with sex-based differences in response. In addition, we recently found that housing at altitude can alter rodent cognitive behavior. MDD is linked to cognitive issues in learning and memory, negative bias and executive function, and hypoxia at altitude may alter cognitive function in MDD and otherwise.
How does the research you do help patients?
Antidepressant treatment-resistance is a critical issue in MDD and anxiety disorders. A significant part of our pre-clinical research involves finding novel effective therapeutics for SSRI-resistant depression and anxiety. MDD is linked to poor brain energy function. We have shown that the bioenergetic compounds creatine and cyclocreatine improve rodent brain energy function and can be effective treatments for SSRI-resistant depression and anxiety. Creatine is antidepressant in only female rats but not males, and similarly, in humans, creatine treatment improves human brain energetics and reduces the brain energetic deficit in women with MDD. Cyclocreatine however is effective for both depressive and anxiety symptoms in rats of both sexes. We have ongoing studies testing other novel compounds for efficacy in this model. One of the benefits of being part of HMHI is the potential of collaborating with clinical researchers to initiate clinical trials of compounds that are found to be effective in our animal model.
What research are you hoping to work on next?
We recently received funding from the HMHI/HCI Partnership Seed Grant in collaboration with Dr. Randy Jensen at HCI. Glioma patients suffer from MDD and anxiety, which often persist even after effective treatment of the cancer. Using Dr. Jensen’s rodent glioma model, we will test the bioenergetic compound cyclocreatine as a novel therapeutic for both the brain tumor and related depressive and anxiety symptoms. Cyclocreatine improves energetic function in the brain, has anti-tumor activity in animal models, and improves depressive and anxiety symptoms in our model. We are excited to be starting these studies this month! I am also interested in expanding our cognitive studies to explore impacts on cognitive function which may not be involved in MDD. Furthermore, I am interested in studying how aging affects the impact of living at altitude on mental health and cognitive function. In addition, I am interested in studying the impact of living at altitude on the gut microbiome. The gut microbiome is a term used to describe the multiple types of bacteria and other microorganisms which live in the intestines. Interactions between the brain and the gut microbiome are highly linked to depression, and studying the microbiome could lead to novel therapeutic options for MDD.
What are you passionate about outside of work?
Before moving here, a friend surprised me by saying “I guess Utah’s ok if you like that lunar landscape kind of thing”. Turns out I adore the Utah landscape and love bumming around Southern Utah. I enjoy hiking or kayaking in the mountains or around the Great Salt Lake. Another big draw for me locally is the Sundance Film Festival. I also have a thriving life as an artist- I paint watercolors and make pottery, and love to exhibit my art. I have an exhibit opening at Red Butte Gardens the end of this month! I also enjoy gardening, cooking and entertaining and listening to live music.