Arubala Reddy explains her newest research and her hope for a world without Alzheimer’s disease.
Arubala Reddy hopes, in 20 years, Alzheimer's disease will be cured and she will have played a role in it.
You see, she's been working on it for more than 20 years already.
Reddy began her neurotransmitter and mental health research in 2001 at the Oregon National Primate Research Center, where she focused on depression, obesity and the mental health of nonhuman primates. Her work there led her to realize the complicated interplay between depression and dementia. Since moving to the Texas Tech University Health Sciences Center (TTUHSC) in 2014 and Texas Tech University five years later, she has worked to discover the cellular and molecular mechanisms of Alzheimer's disease.
But she's not just a researcher.
Each year, she participates in the Alzheimer's Association's Walk to End Alzheimer's. She stops in the Promise Garden to see the orange, yellow, blue and purple flowers representing all those who have been affected by Alzheimer's disease and other forms of dementia. Each year that passes, the flowers in the Promise Garden remind her of the work that remains.
For her, it's the white flower that's most powerful. It represents hope for a world without Alzheimer's.
Ahead of this weekend's 2022 Walk to End Alzheimer's, Reddy tells us about the latest developments in her research – including a five-year, $2.6 million grant from the National Institute on Aging – and where she hopes her work will lead.
We have previously written about your work with citalopram and its effects on Alzheimer's disease. Tell us about the research this new grant will fund. What are you studying?
I received a new five-year RO1 grant from National Institute on Aging, part of the National Institutes of Health, called “Serotonin neuromodulation in 3Ds: Depression, Diabetes and Dementias.” This grant is about studying the molecular mechanisms of the neurotransmitter serotonin in dementia and its interlinks between depression, diabetes and dementia.
Our newly funded grant started in February and ends in January 2027, meaning I will have a job at Texas Tech doing serotonin science for the next five years. I'm relieved I will get to study my passion and focus on the science of serotonin. In the past, I have received funding from the Alzheimer's Association (a two-year Investigator Initiated Research grant and three years for sex and gender in Alzheimer's disease), National Institutes of Health (a three-year grant) and the Garrison Family Foundation, which supported my full salary and research supplies to continue brain science.
What questions are you trying to answer?
Currently, we do not have a complete understanding of serotonin changes that occur in healthy brains and how these alter in Alzheimer's disease brains.
Dementia is complex, heterogeneous, multifactorial condition with aging as a major risk factor, and depression and diabetes/obesity onset make it more complex. The brain demands glucose, but systemic organs do not; when you put patients on diabetic intervention, the brain drops energy cellular energy metabolism. Depression is another story; it has been known for many years that neurotransmitter loss is a causal factor for 80% of depression, and every form of dementia has low neurotransmitters, especially serotonin. I have studied serotonin in the subcortical brain for the last 20 years. At the cellular and molecular level, we see changes in neuroprotection and added neural resilience. We have also reported the benefit of serotonin in nonhuman primate models, rodent models and human clinical trials by others.
However, there are still some unanswered questions about how serotonin affects so many physiological processes. I think I am close to answering it, and that is what we are working on for this grant: how serotonin affects cellular mechanisms canonically and noncanonically in relation to depression, dementia and diabetes/obesity.
What do you hope this research will accomplish?
The subcortical brain is not studied much in neurological disorders. Our objective is to establish the connection of the pivotal brain area connecting the central nervous system, brain and blood-brain barrier. Research into serotonin synthesis in the subcortical raphe area unfolds the intracellular pathology in what I call the 3Ds: depression, diabetes and dementias. This five-year funding will allow us to establish strong links in the 3Ds. This will allow more training opportunities for people interested in the research. And by the last year of the grant, we will definitely be able to find multiple avenues for new therapeutic targets and disease development.
You are the only female researcher at Texas Tech currently funded by a five-year R01 grant through the National Institutes of Health. To you, what does that say about the importance of this research?
I was pleasantly surprised when I was told I had created a history at Texas Tech! I laughed as I don't think it happened without my support team's assistance.
Without a doubt, if the chair of nutritional sciences, Dr. Nikhil Dhurandhar, and the dean of the College of Human Sciences, Dr. Tim Dodd, did not let me have the lab on the fourth floor, it might not have happened. Dr. Dodd and Dr. Dhurandhar are visionary scientists who helped me succeed. I submitted this grant with two of my colleagues, Dr. Vijay Hegde and Dr. Andrew Shin, who are also interested in similar research, so we have a strong team. Dr. Dhurandhar and Dr. P. Hemachandra Reddy, the vice chair for research in internal medicine at TTUHSC, are consultants on this grant. I cannot believe I have such a great team. I also have passionate lab personnel, who brainstorm and conduct the lab work efficiently.
As a woman researcher hailing from India, my learning curve was self-motivation. I came from a Hindi medium school, and in sixth grade, when I presented Mendelian genetics, I was mocked for writing chromosome as “chronosone.” I was not very happy; I asked my parents if I could learn science from an English medium, and I moved on to reading a lot. I always had great mentors and an encouraging family, especially my mom and my husband. I lost my mom to COVID-19 in April 2021, and when I got this grant, I cried a lot because she was always supporting me, saying, “Don't worry; you will get it.” She was there when I submitted it and was not there when I got it.
As a woman, I always feel we get shortchanged, undermined and put down because it is a minority to be a woman scientist. But in 2019, I joined Texas Tech, and I think I made the right choice. I was pleasantly shocked by how cooperative, supportive and efficient the Office of Research & Innovation is. Every unit – the Institutional Biosafety Committee, the Animal Care and Use Committee, Grants administration, IT support in the College of Human Sciences – is supportive. Everyone helped immensely! After grant submission, we had one opportunity to submit additional just-in-time information I remembered; Amy Cook and I were working on a Sunday to submit the documents. This is the kind of involvement from others that made it possible. My grant administrator, Olivia Martinez, and Cui Romo always accept my transient anxiety during grant submission and overlook it. I emphasize the process and people because they all made it possible – good science alone cannot survive. For me, the people I mentioned are the core of Texas Tech, who are doing their job but made a massive change in my life.
My husband, Hemachandra, is beyond any imagination and steps in when I say “I quit.” He will not let me and keeps reminding me of my words – that I owe my success to my parents and siblings, and I cannot disappoint them. That is my motivation. I want to praise woman scientists everywhere, and I am very vocal about it. When I was transitioning to Texas Tech, two of the women grant administrators who barely knew me stood up for me. I was amazed by their strength, given to me; they refused to accept grants I returned to them and encouraged me to work to make the applications stronger. I have seen firsthand the sacrifices you make to be a woman scientist. I also want to encourage women to come out and get more involved in research. We are innately analytical, organized, multitasking and passionate. These are some required skill sets for research.
Getting this grant boosted my confidence, which had been racked from past years. I can help put my home institution on the global map. I am pleased with Texas Tech and want to give back by training stronger, dedicated researchers in neuroscience and nutrition. This opens new avenues to get more grants and open labs to enthusiastic young and older minds. Right now, I work with underage students at Lubbock High and summer interns from out of town to explore clinical research. I also am a member of the Alzheimer's Association Advisory Board and get to showcase my research at public forums. Working with the advisory board is a humbling experience for me because I see why I have to be a responsible and severe researcher, because a lot depends upon what I say and discover.
How did you begin studying Alzheimer's disease? Was there a particular case or person in your life that brought it home?
I did not have a particular dementia in my biological family. I came from a priest family, and a healthy lifestyle and discipline are essential to me. (My father still preaches the benefits of a healthy lifestyle and exercise – he is a lifetime prime member of the Indian Body Building Association.) Seeing him active, my outlook changed to look at Alzheimer's disease differently. Singing and chanting helps relieve stress because it improves serotonin function. Scientifically, serotonin is connected to happiness. So, I started my reverse journey on how this can help with the neuropsychiatric symptoms of dementia.
This concept evolved in 2014 when I left my permanent job in Oregon and moved to Lubbock, following my husband. I was unsuccessful in finding a job and feeling useless. I knew I had many skills and could help any principal investigator conduct successful research, but I took up the challenge and found a neuropsychiatric and neurodegenerative connectivity to serotonin.
Let's get hypothetical for a minute. Suppose that in 20 years, Alzheimer's disease has been cured completely. What role do you want to have played in that?
I love this question because this is what we are aiming for. This Saturday (Nov. 5) is ENDALZ, the walk to end Alzheimer's. I always participate and support the walk. One very emotional aspect of the walk is the Promise Garden filled with orange, yellow, blue and purple flowers. In the Promise Garden, orange flowers represent individuals who support the vision of Alzheimer's disease research, yellow is for those who care for Alzheimer's disease patients, blue is for those living with Alzheimer's and purple is to honor someone we lost to it. We carry one white flower and hope that, one day, someone will have a chance to plant it. The white flower of hope represents the world without Alzheimer's disease. I hope we get to see more white flowers in the Promise Garden.
This journey every year makes me very emotional. I cry, but then I retrieve strength from my emotion and prepare for a positive journey for next year. I know we will have breakthroughs through new research and drug availability for Alzheimer's disease. My role will be that I have contributed to the Promise Garden by staying healthy, discovering the role of happy molecules in 3D and being proud of it. I have encouraged many young minds to do Alzheimer's disease research or clinical research. I am the perfect example of where diversity hinders, combats and benefits research. If I can do research, anyone can do it.
Is there anything else you'd like to say?
At present, my goal is definitely to continue my research with full dedication. I want to continue to acquire more funding to support more students in my lab. I am at the point in my life where I work with students in the lab to combat the issues, which allows students to learn firsthand and get confident.
I had an excellent mentor for my Ph.D., Dr. Cynthia Bethea. She told me the first day that she wanted to see me as an expert in serotonin research. I am not sure if it was a joke or if she seriously thought I could do it, but I am still learning every day.
I think I have two personalities in my brain: one is serious about what I do in research, and the other one likes to learn and explore. If I find some connection to a certain finding, the first person I call is my husband and take a full 30 minutes to explain the “I told you so” version of it. I am not shy about reaching out to people and praising their work, whether it is in research or another area. I have no on/off switch for my research; it is always on my mind. I am openly biased toward girls in science and am always willing to help and make room for one any day. I don't compromise any science but I am willing to help anyone, because someone always helped me when I was learning.
