Posts tagged with "PhD"

Business woman article illustration by Kaelen Felix for 360 Magazine

Ask Better Questions

Advice from a Researcher on How to Make Research Your Business’s Superpower

By: Kirsten Lee Hill, PHD.

When I talk to people about research, the first thing I notice is that almost everyone is doing research–they just don’t call it that.

Put simply, research is creating an intentional plan to answer a question you have, and then putting it into action. As a business owner, I’m willing to bet that you have questions you would like answered. Questions like:

  • How are people experiencing my products/services?

  • Does my product/service work?

  • How can I improve my product/service?

On a daily basis as you continue to run your business and make decisions about growing or pivoting, you are using information to answer these types of questions. Every time you ask a customer for feedback, send out a poll, or look at records to make decisions about products or services–that’s research!

The quality of the information you get is only as good as the quality of the questions you ask. The key to good research is asking good questions, and crafting good questions is both an art and a science.

To create a good question, you have to get specific about what it is you want to know.

Have you ever asked a client or customer if they are “satisfied?” Or, has anyone ever asked you if you are “satisfied” with their product or service?

Personally, it is my least favorite question, and one that I never ask.

Here’s the thing–I never ask if someone is satisfied because I don’t care. Not asking is strategic. To me, that question is a waste of space (and my clients’ goodwill), and I want to use space and goodwill on important questions that matter to me. Big, vague words like “satisfaction” are not helpful in evaluating my work or making decisions.

What does it even mean to be satisfied?

In some sense it means that I generally did a good job or a bad job. But, I don’t make decisions based on ambiguous terms. I want specific insights to drive my business.⁠

Specific insights come from specific questions.

So, instead of asking if someone is “satisfied” for if they “liked” your product/service, choose an area(s) of feedback that would provide meaningful information. Perhaps you want to know if your product was useful, made something easier, or fun. If you’re selling a new shirt and people say they hate it, that’s not helpful. Instead, ask specific questions about the color, fit, and fabric so that you can take action on the feedback.

Questions are powerful tools that can provide you with information to make important decisions. Don’t waste them.

To learn more about Kirsten Lee Hill, visit her website.

Prostate cancer illustration by Heather Skovlund for 360 Magazine

Battle Against Prostate Cancer

New Insights into Hormone’s Action Could Help in Battle Against Prostate Cancer

Discovery Sheds Light on How Cancer Cells Use Androgen

Researchers at UVA Cancer Center have unveiled important new insights into how hormones known as androgens act on our cells – and the discovery could boost efforts to develop better treatments for prostate, ovarian and breast cancers.

The findings shed light on how androgens interact with their receptors inside cells to affect gene activity. This process is important in both healthy cells and certain cancers. Hormone therapy for prostate cancer, for example, aims to reduce the amount of androgen in the body, or to stop it from fueling the cancer cells. However, the approach does not work for some men, and for others it eventually fails. So, scientists are eager to better understand how our cells – and cancer – interact with androgen.

“Our study reveals a new mechanism for how androgen regulates communication within prostate cancer cells,” said Bryce M. Paschal, PhD, of the UVA School of Medicine’s Department of Biochemistry and Molecular Genetics. “Anti-androgen therapies continue to be the cornerstone for prostate cancer therapy. The better we understand how androgens work, the better clinicians will be positioned to understand why it fails, and how even better therapies can be designed.”

Androgen and Cancer

In a new paper in the scientific journal Nature Communications, Paschal and his colleagues describe how a complex signaling system regulates androgen receptor activity. The system, they found, uses a “writer” and a “reader” to modify cellular proteins – sort of like how a computer reads and writes information.

Scientists have appreciated the importance of these modified proteins but understanding just how they influence the androgen receptors has been difficult. One key to the regulation process, found by Paschal and his SOM team, is an enzyme, Parp7, produced by the PARP7 gene. Parp7 is part of a family of enzymes involved in important cellular functions including DNA repair.

Certain cancer drugs already target certain Parp enzymes; these drugs are used to treat prostate, ovarian and breast cancers in patients who have mutations in DNA-repair genes. And while androgens are usually discussed in the context of prostate cancer, androgens may be important in ovarian and breast cancer as well.

Paschal’s new findings offer fresh insights into these Parp drugs and could lead to improved treatments that help patients get the best outcomes. Further, Paschal and his team found lower levels of Parp7 in prostate cancer that has spread to other parts of the body than in the initial tumors. That may suggest that a reduction in Parp7 is associated with the progression of the disease, the researchers say.

With their new androgen insights, Paschal and his colleagues have provided scientists with important new directions to explore in the battle against prostate and other cancers.

“Our next steps will be to use pre-clinical models to determine the role this pathway plays in prostate cancer progression, and whether inhibition of the pathways slows disease,” Paschal said. “We are very excited by what we have learned thus far. Our study emphasizes there is still so much to be learned, and that basic science plays a critical role in defining the molecular context for enzyme and drug action. “

About the Research

The research team consisted of Chun-Song Yang, Kasey Jividen, Teddy Kamata, Natalia Dworak, Luke Oostdyk, Bartlomiej Remlein, Yasin Pourfarjam, In-Kwon Kim, Kang-Ping Du, Tarek Abbas, Nicholas E. Sherman, David Wotton and Paschal.

The work was supported by the National Institutes of Health’s National Cancer Institute, grant CA214872.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Mental Health Awareness illustration by Heather Skovlund for 360 Magazine

Mental Health Awareness

Many people, including children and adults across diversity backgrounds, can struggle with social, emotional, cognitive, and behavioral health. These challenges can be situational, present for a season of life, or be a struggle across a lifetime. The symptoms may also turn on and turn off, be persistent every day, or resolve just to pop back up again.

Even though having complications with mental or behavioral health is common, it does not necessarily mean a person is functioning at their best or the symptoms should be left unaddressed. Early intervention can be more effective, than the choice to put off addressing a mental health concern for another time.

Awareness of mental health signs and symptoms are important. The first step is recognizing when we need support. Let’s set aside labels such as depression, anxiety, addictive behaviors, and disorders for a moment. Instead, let’s consider observations. Below is a clustered list of commonly experienced struggles we can lookout for to monitor our mental health:

Socially

  • Noticing a pattern of withdrawing or avoiding friends, family, or activities
  • Having interpersonal conflicts with friends, family, colleagues, neighbors, or even strangers
  • Having a difficult time understanding and/or relating to others or common life scenarios
  • Feeling disconnected from others or struggling to get close to others
  • Feeling lost about knowing who you are

Emotionally

  • Experiencing sadness, despair, distress, prolonged sorrow
  • You or others noticing changes in your mood from high to low
  • Enduring excessive worry, fears, or discomfort with the unknown
  • Experiencing extreme guilt, self-blame, or negative self-talk
  • Having bouts with excessive or persistent anger

Cognitive/Thinking

  • Noticing thought patterns that are confused, conflicted, indecisive, repetitive, or forgetful
  • Having a lowered ability begin or maintain focus
  • You or others noticing a disconnect between your thoughts and the world around you
  • Feeling fearful such as paranoia
  • Having repeat unpleasant or worrisome thoughts or images
  • Hearing, seeing, or feeling something that is not truly there
  • Thoughts of hurting or killing yourself or someone else

Behavioral

  • Having a reduced ability to cope or resolve daily living complications or stress
  • Struggling with adjustment to life changes
  • Experiencing problems related to alcohol, tobacco, and/or legal or illegal substances
  • Noticing changes in eating habits such as too much, too little, overly focused on eating
  • Observing patterns of overexercise
  • Changes in sex drive
  • Having episodes of violence towards others, yourself, animals, or objects
  • Challenges with impulsive decisions or risk taking

Physical

  • Seeing trends in energy level such as significant tiredness or grand amount of energy
  • Struggles falling asleep, staying asleep, waking up, or low quality of sleep
  • Having physical symptoms such as stomach pain, back pain, headaches, heart pounding, shortness of breath, or other unexplained physical symptoms
  • Experiencing medical providers do not take your symptoms seriously enough

Experiencing one or a few of these symptoms at one time may be a part of life based on the amount of lemons life just handed you. However, there may be a mental health concern worth seeking proper care for if you experience one or more of these symptoms for a short or an extended period of time. Due note, some symptoms are more serious than others, such as harm to yourself or someone else, that should not be ignored and need care immediately.

Another element we can use to monitor our mental health is awareness of how our mental health symptoms interact with our daily lives. Sometimes mental health struggles can become disruptive to daily life such as negatively impacting relationships with others, how you think or feel internally about yourself, employment, housing, finances, and/or legal issues. Other symptoms are manageable and do not cause a large disruption; however, beware some symptoms can fly under the radar, but that does not necessarily indicate all is well.

If you are unsure if you are experiencing mental health concerns and would like a better understanding, then consider completing a screener. Mental Health America provides a free, quick, screening tool that provides mental health you can use to make decisions about next steps for care. The results can also be used to start the initial discussion with a mental health provider.

There is hope! In most circumstances, symptoms can be managed, reduced in intensity, and relief increased when working with a mental health provider. There are various forms of care, and you can find the right fit for you such as talk based therapy in-person or online, activity-based therapy, and collaboration with medical providers for mediation as needed.

If you are ready to take the next step, then there are multiple resources available to help you find the right provider. In emergency situations such as thoughts of harming yourself or someone else as well as severe mental illness, then calling 9-1-1, going to a local emergency room, or contacting the National Suicide Prevention Lifeline at 1-800-273-TALK (1-800-273-8255) or using live chat on Suicide Prevention Lifeline  may be the best routes.

In non-emergency situations there are options such as contacting a primary care provider for a referral, reaching out to loved ones, connecting to your religious or spiritual community, or finding a professional provider. Below is a list of resources for locating a provider in your area:

Mental health is just like it sounds….health. It can be scary or there can be a stigma to seek out care. However, removing the stigma, overcoming fear, seeking care, and taking steps to improving life takes courage. But you are worth it, and you deserve a better tomorrow.

Michelle Perepiczka, PhD, LPC (CO), LMHC (NY), RPT-S, NCC

Core Faculty

University of Phoenix

College of Social and Behavioral Sciences

Pregnancy illustration by Heather Skovlund for 360 Magazine

Black Maternal Health Crisis

Free Virtual Webinar During Black Maternal Health Week:

“The Black Maternal Health Crisis in the United States”

As this unpredicted season begins against the backdrop of Covid-19, racial unrest, and action for justice and healing – nothing is normal. The Promise Heights From the Heights virtual series will look at the challenges of the moment, offering actionable insights that you can use today. 

The third of these freevirtual webinar conversations is scheduled for Monday, April 12, 2021 from 2-3:30 pm, and will feature a message from Congresswoman Lauren Underwood, representing the 14th District of Illinois as the first woman, the first person of color, and first millennial to represent her community in Congress, and also the youngest Black woman to serve in the United States House of Representatives. The Black Maternal Health Caucus was launched by Congresswomen Alma Adams and Lauren Underwood to improve Black maternal health outcomes and to raise awareness within Congress about the problem and advocate for effective, evidence-based, culturally component policies and best practices for health outcomes for Black mothers.

Also joining our conversation, moderated by Reporter Tatyana Turner of The Baltimore SunL. Latéy Bradford, MD, PhD, University of Maryland Medical Center: Chief Resident, Family Medicine; Stacey Stephens, LCSW-C, Director, B’more for Healthy Babies, Promise Heights; and Stephanie Etienne, CNM, Certified Nurse Midwife based in Baltimore.
 

ABOUT THIS EVENT:
As stated in the Black Maternal Health Caucus/Momnibus website, “In the richest nation on earth, moms are dying at the highest rate in the industrialized world—and the rate is rising. For as dire as the situation is for all women, the crisis is more severe for Black mothers.”  More recently, the March 11, 2021 New York Times featured story, “Why Black Women Are Rejecting Hospitals in Search of Better Births” reported that, “Black mothers in the United States are 4 times as likely to die from maternity-related complications as white women.”

Black women also experience higher rates of maternal complications and infant mortality. They are twice as likely to lose an infant to premature death, and these disparities have not improved in more than 30 years. These disproportionate inequities exist regardless of income, educational level or any other demographic characteristic.  This April 12 virtual session will provide insight how to make pregnancy and childbirth safer in the U.S., amplify community–driven policy, practice and systems and enhance community organizing on Black maternal health by taking action to reduce maternal mortality and reduce morbidity related to childbirth. 
 

Click here to learn more and register for this free program

To learn more about the From the Heights series of virtual events, click here.

Funding for the From the Heights series was provided by The Annie E. Casey Foundation and Kaiser Permanente

Child with phone illustration by Heather Skovlund for 360 Magazine

Children and Screens Announces Grant

­CHILDREN AND SCREENS ANNOUNCES $100,000 GRANT SUPPORTING NEW RESEARCH INTO DIGITAL MEDIA USE AND BRAIN DEVELOPMENT

Children and Screens: Institute of Digital Media and Child Development is pleased to announce that it has awarded a grant of $100,000 to Marc Potenza, Ph.D., MD, Professor of Psychiatry at Yale University, Yihong Zhao, Ph.D., member of the Center of Alcohol and Substance Use Studies at Rutgers University, and their interdisciplinary, interinstitutional team, in support of their research exploring the associations between screen media activity and brain development in school-aged children. 
 
“It is vital to investigate what ever-increasing digital media engagement means for developing brains, especially in middle childhood when children’s devices and brains are working on overdrive. Technology is advancing rapidly, and we hope to do our part to help science keep up; we are delighted to create opportunities to advance scientific research on this topic through the Institute, which I founded 13 years ago.” Dr. Pam Hurst-Della Pietra, President and Founder, Children and Screens: Institute of Digital Media and Child Development 
 
Drawing on longitudinal data from the NIH’s landmark Adolescent Brain Cognitive Development Study, Dr. Potenza, Dr. Zhao, and their associates intend to utilize state-of-the-art statistical methodology and predictive modeling to investigate the relationships between digital media use and changes in brain structure and function, as well as the associated clinically relevant behaviors. The study, which was proposed following the Institute’s March 2020 Digital Media and Developing Brain Research Retreat, will examine the effects of a variety of specific media-based activities and will focus on children from ages 9-12. The results of this research will yield benefits and insight not only for the research community, but also for families, clinicians, and policymakers.
 
“The advances in ‘big data’ approaches have led to an unprecedented increase in our understanding of how brain structure and function relate to specific behaviors. With the support of Children and Screens, we aim to apply novel and innovative big data approaches to ABCD data to understand how brain structure and function relate to, and importantly may be impacted by, types and patterns of screen media activity. Dr. Martin Paulus and colleagues used a portion of the first wave of ABCD data to identify patterns of cortical thinning associated with screen media activity. We hope to build off and extend this work by examining the full initial sample and subsequent waves of ABCD data to determine brain-behavior relationships with respect to youth screen media activity. We hope to communicate these findings in order to advance prevention and policy efforts that promote healthy childhood development in environments increasingly involving digital technologies.” – Dr. Marc Potenza, Grant Recipient
 
Bridging the medical, neuroscientific, social scientific, education, and academic communities, the Children and Screens’ interdisciplinary scientific research grants program was conceived as part of a larger research program to advance and support study, knowledge, and scientific collaboration. Developed in 2017, the grants program provides researchers with access to the early-stage financial support necessary to pilot worthy new projects studying the impact of children’s engagement with current and evolving technologies.
 
In addition to the research funds awarded as part of the retreat program and those granted to explore the impacts of digital media during the current health crisis, Children and Screens’ regular Tips for Parents newsletter provides evidence-based, practical advice for families coping with the unprecedented realities of the pandemic, including changed economic circumstances, health concerns, lockdowns, social distancing, remote learning, and working from home. Each newsletter features insights from world-renowned experts, who share tips and advice about managing screen time, social media use, gaming, technology addiction, privacy, parenting, and more.
 
In addition, our popular, bi-weekly Ask the Experts virtual workshop series features dynamic conversations among international, interdisciplinary experts in the field of digital media and child development. Each discussion explores a different digital media challenge associated with the COVID-19 pandemic and presents families with current scientific research, clinical advice, and practical, evidence-based advice. Panelists include leading parenting experts, former AAP Presidents, top child and adolescent psychiatrists, high-impact journal editors, leading researchers, well-known authors, and others. To date, the series has reached parents, researchers, educators, clinicians, government agencies, and public health professionals in over 30 countries and all 50 states.
 
About Children and Screens:
Since its inception in 2013, Children and Screens: Institute of Digital Media and Child Development, has become one of the nation’s leading non-profit organizations dedicated to advancing and supporting interdisciplinary scientific research, enhancing human capital in the field, informing and educating the public, and advocating for sound public policy for child health and wellness.

Film illustration by Heather Skovlund for 360 Magazine

Unforgettable Foreign Films

10 Foreign Films with the Most Unforgettable Love Stories

By Roberta Seret, PhD

I have two loves – literature and film. The most powerful love stories jump off the pages or off the screen, narrating different types of love turmoil, journeying through danger and obstacles to find love. The best love stories occur when love triumphs over evil. 

In the past twenty years, I have taught film through my NGO at the United Nations and at New York University. It is a love story that captures my students the most. Their 10 favorite love stories in foreign films deceit different ways of loving, but they all try to overcome these obstacles to find it. Although they may not always get their happy ending, it’s always worth the risk:

1.     JOJO RABBIT – (New Zealand) 2019, director Taika Waititi. During World War ll, ten-year-old Jojo is being brainwashed as a Hitler Youth. Strangely, his mother allows this, for it is her only way to protect him. We see how deeply a mother loves her son as she prepares him to be independent. Simultaneously, the director expresses his love for the future of children to do what’s right.

2.     HONEYLAND – (Republic of Northern Macedonia) 2019, directors Tamara Kotevska and Ljubomir Stefanov. Nominated for an Oscar for Best Documentary and Best Feature Film, this story recreates a Paradise Lost and its destruction by a greedy man. Love for beauty and nature, and the desire to recapture it, is represented by honey – becoming extinct – and man’s inhumanity to lose it.

3.     NEVER LOOK AWAY – (Germany) 2018, director Florian Henckel von Donnersmarck. Based on the life of the famous painter, Gerhard Richter, the director recreates the artist’s search for Truth. It is only through love for Art that the artist can find peace. It is this tumultuous search that pushes him/her to create.

4.     CAPERNAUM – (Lebanon) 2018, director Nadine Labaki. Lost children, abandoned, hungry, and forced to go against their conscience, are victims of war-torn Lebanon and Syria. The director opens her heart by using her hand-held camera to capture how children suffer in their struggle to survive. It is through her love for these children that we understand and want to help. 

5.     FACES PLACES – (France) 2017, directors Agnes Varda and JR. At 89-years-old and one year before her death, famed filmmaker, Agnes Varda embarks on a road trip to show her appreciation to the people of France. As a token of her deep love, she offers them a new type of art – photos of themselves – while she is making a film of their acceptance. Photography mixes with cinematography, the moving image fuses with still art, to show the director’s love for people and give them Art. 

6.     LION – (India/ Australia) 2016, director Garth Davis. The true story of 5-year-old Saroo, who gets lost on a train in India and cannot communicate in a different dialect to return home. He is placed in an orphanage and adopted by a couple from Tasmania, Australia. Twenty-five years later, his obsession to find his biological mother is proof of his filial love.

7.     TONI ERDMANN – (Germany / Romania) 2016, director Maren Ade. A father loves his ambitious, modern daughter and wants to help her understand what happiness and love are. But the generational gap proves to be stronger than his quest. Despite his struggles and sacrifices, she answers when she sings Whitney Houston’s song, “Learning to love yourself is the greatest love of all.”

8.     PHOENIX – (Germany) 2014, director Christian Petzold. Nelly survives World War II because she is obsessed at Auschwitz to be loved again by the man she loves. She does return to him but disfigured, and he does not recognize her. Deceitfully, he schemes to help her survive the traumas of her past. But as she learns the truth, will her love forgive him?

9.     IDA – (Poland) 2013, director Pawel Pawlikowski. Ida embarks on a spiritual journey to choose between a life of love and family, or God and religion. As she voyages toward the answer, she learns about her history and what the material world can offer. But she keeps repeating, “And then?” She realizes it is love for God and the spirit that can offer her the truest love.

10.  CASABLANCA – (USA/ Morocco) 1942, director Michael Curtiz. This is the best love story of all. For those who will see this film for the first time, I am jealous. This is an American movie made in Morocco with an anti-Hollywood ending. It shows and answers what is true love? What we see on the screen is a love that hurts – for all of us. And yet, love must be experienced, and this film must be seen!

Roberta Seret, Ph.D., is the director of Advanced English and Film at the United Nations for the Hospitality Committee and Founder of the NGO at the United Nations, International Cinema Education. She is the author of the Transylvanian Trilogy, with Love Odyssey releasing March 23, 2021. Visit her website for more information.

AC_LatinoCovid by Allison Christensen for 360 Magazine

Antibody Cocktail May Prevent Symptomatic COVID-19 Infections

An antibody cocktail being tested at UVA Health and other sites was able to block 100% of symptomatic COVID-19 infections among people exposed to the virus, early results from the clinical trial suggest.

In addition, those who developed asymptomatic infections accumulated far less virus in their bodies than usual and saw their infections resolve within a week, according to interim data released by the cocktail’s manufacturer, Regeneron Pharmaceuticals.

“This is the first treatment shown to prevent COVID-19 after a known exposure, and offers protection for unvaccinated individuals caring for a family member with COVID-19,” said UVA Health’s William Petri Jr., MD, PhD, one of the leaders of the trial at UVA. “We expect that Regeneron will file for Emergency Use Authorization from the FDA so that this drug can be used outside of the context of a clinical trial.”

Antibodies for COVID-19

The phase 3 clinical trial aims to determine if the antibodies will prevent COVID-19 infection in people who have been exposed but not yet developed the disease. This is known as “passive immunization.”

Regeneron’s new analysis, which has not yet been published in a scientific journal, looked at outcomes in approximately 400 trial participants. Of 186 people who received the antibodies, none developed symptomatic COVID-19. Of the 223 who received a placebo, eight developed symptomatic COVID-19, the company reports.

Asymptomatic infections occurred in 15 of the antibody recipients and in 23 of the placebo recipients. Overall rates of infection, including both symptomatic and asymptomatic infections, were approximately 50% lower in the antibody group.

Among those who developed infections, placebo recipients had, on average, a peak viral load (the amount of virus in the body) that was more than 100 times greater than antibody recipients. The antibody group also recovered more quickly–all the infections resolved within seven days, while 40 percent of infections in the placebo group lasted three to four weeks, Regeneron said.

The cocktail also appears to shorten the duration of viral shedding, the time when the virus is being manufactured in the body. The viral shedding period was nine weeks among antibody recipients and 44 weeks among the placebo recipients. While people with COVID-19 are not infectious for this entire time, reducing the duration of viral shedding may shorten the period when they can spread the disease.

There were more adverse events reported among placebo recipients than among antibody recipients – 18 percent and 12 percent, respectively. Regeneron attributed this to the larger number of COVID-19 infections in the placebo group.

There was one death and one COVID-19-related hospitalization in the placebo group and none in the antibody group. Injection-site reactions were reported among 2 percent of both groups.

“We are profoundly grateful to the nurses and staff of the UVA COVID-19 clinic, led by Dr. Debbie-Anne Shirley,” Petri said. “Their day-to-day support made our participation in this trial possible.”

About the Clinical Trial

Phase 3 clinical trials, such as the one under way at UVA, examine the safety and effectiveness of new drugs and treatments in large numbers of people. Positive results in the phase 3 trial could spur the federal Food and Drug Administration to make the antibody cocktail available for post-exposure COVID-19 prevention.

The antibody cocktail is not a vaccine and is not expected to provide permanent immunity to COVID-19.

The team conducting the study at UVA is led by Petri and Shirley and includes Gregory Madden, MD; Chelsea Marie, PhD; Jennifer Sasson, MD; Jae Shin, MD; Cirle Warren, MD; Clinical Research Coordinator Igor Shumilin; assistant Rebecca Carpenter; and COVID-19 Clinic nurses Michelle Sutton, Elizabeth Brooks, Danielle Donigan, Cynthia Edwards, Jennifer Pinnata, Samantha Simmons and Rebecca Wade.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Woman at Computer by Mina Tocalini for 360 Magazine

UVA’s DNA Discovery

Scientists have identified a group of drugs that may help stop a leading cause of vision loss after making an unexpected discovery that overturns a fundamental belief about DNA.

The drugs, known as Nucleoside Reverse Transcriptase Inhibitors, or NRTIs, are commonly used to treat HIV. The new discovery suggests that they may be useful against dry macular degeneration as well, even though a virus does not cause that sight-stealing condition.

A review of four different health insurance databases suggests that people taking these drugs have a significantly reduced risk of developing dry macular degeneration, a condition that affects millions of Americans.

“We are extremely excited that the reduced risk was reproduced in all the databases, each with millions of patients,” said Jayakrishna Ambati, MD, a top macular degeneration researcher at the University of Virginia School of Medicine. “This finding provides real hope in developing the first treatment for this blinding disease.”

Targeting Macular Degeneration

The new discovery comes from Ambati; Fred H. Gage, PhD, of the Salk Institute for Biological Studies; and collaborators around the world. The work rewrites our understanding of DNA, revealing for the first time that it can be manufactured in the cytoplasm of our cells, outside the cell nucleus that is home to our genetic material.

The buildup of a certain type of DNA in the cytoplasm, Alu, contributes to macular degeneration, the researchers found. This buildup appears to kill off an important layer of cells that nourishes the retina’s visual cells.

Based on this discovery, the researchers decided to look at drugs that block the production of this DNA, to see if they might help prevent vision loss. They analyzed multiple U.S. health insurance databases – encompassing more than 100 million patients over two decades – and found that people taking NRTIs were almost 40% less likely to develop dry macular degeneration.

The researchers are urging further study to determine if these drugs or safer derivatives known as Kamuvudines, both of which block a key inflammatory pathway, could help prevent vision loss from dry macular degeneration.

“A clinical trial of these inflammasome-inhibiting drugs is now warranted,” said Ambati, the founding director of UVA’s Center for Advanced Vision Science. “It’s also fascinating how uncovering the intricate biology of genetics and combining it with big data archeology can propel insights into new medicines.”

Ambati, of UVA’s Department of Ophthalmology, previously determined that NRTIs may help prevent diabetes as well.

Findings Published

The researchers have published their findings in the scientific journal PNAS. The research team consisted of Shinichi Fukuda, Akhil Varshney, Benjamin J. Fowler, Shao-bin Wang, Siddharth Narendran, Kameshwari Ambati, Tetsuhiro Yasuma, Joseph Magagnoli, Hannah Leung, Shuichiro Hirahara, Yosuke Nagasaka, Reo Yasuma, Ivana Apicella, Felipe Pereira, Ryan D. Makin, Eamonn Magner, Xinan Liu, Jian Sun, Mo Wang, Kirstie Baker, Kenneth M. Marion, Xiwen Huang, Elmira Baghdasaryan, Meenakshi Ambati, Vidya L. Ambati, Akshat Pandey, Lekha Pandya, Tammy Cummings, Daipayan Banerjee, Peirong Huang, Praveen Yerramothu, Genrich V. Tolstonog, Ulrike Held, Jennifer A. Erwin, Apua C.M. Paquola, Joseph R. Herdy, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Shaban Darwish, Ramendra K. Singh, Saghar Mozaffari, Deepak Bhattarai, Kyung Bo Kim, James W. Hardin, Charles L. Bennett, David R. Hinton, Timothy E. Hanson, Christian Röver, Keykavous Parang, Nagaraj Kerur, Jinze Liu, Brian C. Werner, S. Scott Sutton, Srinivas R. Sadda, Gerald G. Schumann, Bradley D. Gelfand, Fred H. Gage and Jayakrishna Ambati.

Jayakrishna Ambati is a co-founder of Inflammasome Therapeutics, iVeena Holdings, iVeena Delivery Systems and DiceRx; a full list of the authors’ disclosures is included in the paper.

The research was supported by UVA’s Strategic Investment Fund, the National Institutes of Health Director’s Pioneer Award, the National Institutes of Health’s National Eye Institute and many other generous contributors. A full list is included in the paper.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

Science Tech Illustration by Gabrielle Archuleta

Blood Discovery Research x UVA

Blood Discoveries Advance Effort to Grow Organs, Battle Cancer 

New Research Reveals Important Insights Into How Our Bodies Make Blood 

CHARLOTTESVILLE, V.A.– Pioneering research into how our bodies manufacture the cells that make blood has moved us closer to regrowing tissues and organs. These findings also may let doctors grow the cells for transplantation into people to battle cancer, blood disorders and autoimmune diseases.

Researcher Karen K. Hirschi, PhD, of the Department of Cell Biology and Cardiovascular Research Center at the University of Virginia School of Medicine, has developed a simple and efficient way to generate “hemogenic endothelial cells.” These cells are the first step in the production line of blood cells, and Hirschi’s new findings provide a blueprint for creating them outside of the body.

“By studying how hemogenic endothelial cells develop normally, we gain the insight needed to generate them in the lab,” Hirschi said. “Now that we have established a method to produce human hemogenic endothelial cells outside of the body, we will continue to improve their production and function as we learn more about the mechanisms that promote their normal development.”

Building Blood-Making Factories

Hirschi’s latest work, published in a pair of scientific papers, offers important insights into how hemogenic endothelial cells form, and how they ultimately give rise to the cells that directly manufacture blood.

Writing in the prestigious journal, Science, she and her team reveal a key trigger that causes the endothelial cells to “transdifferentiate,” or turn into blood-making factories, during embryonic development. These blood-making (i.e. hemogenic) endothelial cells generate hematopoietic stem and progenitor cells (HSPCs) that have long been used for the treatment of cancer and other diseases. Typically, they are taken from sources such as an individual’s bone marrow, but doctors would like to be able to manufacture them quickly and easily for patients on demand. “Generating human hemogenic endothelial cells in the lab from each patient that needs HSPC is the first step toward patient therapies for blood disorders,” Hirschi said.

In a paper published nearly simultaneously in Cell Reports, Hirschi unveils a blueprint for creating the hemogenic endothelial cells, the source of HSPCs, outside of the body. The secret is a substance called retinoic acid. You may have heard of retinoic acid in association with beauty products, but in this case its responsibilities include triggering genes to cause “hematopoietic transition”–to put more vascular endothelial cells in the business of making blood by producing HSPCs.

The new insights provided by the work “will improve our ability to apply developmental insights to the generation of distinct endothelial cell subtypes for tissue engineering and regenerative medicine,” the researchers write in their new paper. “In addition, our system could likely be developed further to optimize the generation of transplantable HSPCs from human hemogenic endothelial cells for clinical therapies.”

The approach offers several advances over existing means, including being quicker and less expensive, the researchers note.

“We hope our continued efforts will move us closer to treating both vascular and blood disorders,” Hirschi said. “These studies highlight the importance of basic cell and developmental biology research as a foundation for devising strategies for patient-specific clinical therapies.”

Hirschi was recruited from Yale in 2019 to join the faculty in the Department of Cell Biology, which has long been interested in addressing how embryos develop and applying this basic knowledge to the repair and regeneration of damaged tissues and organs.

Findings Published

The Science paper was authored by Dionna M. Kasper, Jared Hintzen, Yinyu Wu, Joey J. Ghersi, Hanna K. Mandl, Kevin E. Salinas, William Armero, Zhiheng He, Ying Sheng, Yixuan Xie, Daniel W. Heindel, Eon Joo Park, William C. Sessa, Lara K. Mahal, Carlito Lebrilla, Hirschi and Stefania Nicoli. The work was supported by the National Institutes of Health (grants F32HL132475, U54DK106857, 1K99HL141687, R01HL130246, R56DK118728, R01HL146056. R01HL128064, R01DK118728 and R01GM049077) and the American Heart Association (grants 19PRE34380749 and19TPA34890046).

The research team responsible for the Cell Reports paper consisted of Jingyao Qiu, Sofia Nordling, Hema H. Vasavada, Eugene C. Butcher and Hirschi. That work was supported by NIH grants HL128064, U2EB017103, R01-AI130471 and R01-CA228019; CT Innovations grant 15-RMB-YALE-04; Department of Veterans Affairs Merit Review award I01BX002919; the Swedish Society for Medical Research; and a Stanford Dean’s Fellowship.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

Gym Illustration by Rita Azar for 360 Magazine

UVA on Battling Diseases by Exercise

A top exercise researcher and colleagues at the University of Virginia School of Medicine have launched an ambitious effort to understand the whole-body benefits of exercise so that doctors can use that information to prevent and treat disease.

Zhen Yan, PhD, and his collaborators aim to identify the sources, functions and targets of the molecules that provide exercise’s well-documented health benefits. By understanding this, doctors will better understand how exercise helps fend off disease, and they may be able to design drugs to mimic those benefits for people who cannot exercise, such as those with limited mobility. The cutting-edge research could open new doors both for preventing and treating many common illnesses, the researchers hope.

“No one would dispute that physical activity or regular exercise is the best measures for health promotion and disease prevention,” said Yan, director of the Center for Skeletal Muscle Research at UVA’s Robert M. Berne Cardiovascular Research Center. “In fact, the health benefits of exercise are way beyond our imagination. The underlying reasons for the superb health benefits of exercise are being uncovered by many talented and passionate scientists around the world.”

Understanding How Exercise Improves Health

The UVA researchers have recently joined a national consortium seeking to create a “molecular map” of exercise benefits. Known as the Molecular Transducers of Physical Activity Consortium, or MoTrPAC, the group includes researchers at top institutions across the country, including Harvard, Duke, Stanford and Mayo Clinic.

The consortium came about after the National Institutes of Health invited Yan and a dozen other prominent scientists to a roundtable discussion in 2010 about the future of exercise research and the obstacles that stood in its way. The NIH then set aside almost $170 million for MoTrPAC’s research – believed to be the agency’s largest-ever investment into the mechanisms of how physical activity improves health and prevents disease.

“The program’s goal,” Yan explained, “is to study the molecular changes that occur during and after exercise and ultimately to advance the understanding of how physical activity improves and preserves health.”

The consortium is looking at exercise benefits in both humans and animal models. Initial animal research was conducted at Harvard, the University of Iowa and the University of Florida. In the latest round, UVA is joined by the University of Missouri, the University of Kansas Medical Center and the University of California, Los Angeles.

The vast amount of information collected as part of the project so far has poised the UVA team to make “unprecedented” advances, Yan reports. He and his multi-disciplinary team will employ advanced computer algorithms to sift through the heaps of data to identify specific molecules to study. They will then conduct state-of-the-art research in lab mice using gene editing, combined with a wide range of functional assessment, including muscle, cardiac, metabolic and cognitive/mental functions. This will let them determine the effects the molecules have and lay a foundation for doctors to harness the molecules to benefit human health in the future.

Yan’s team will work closely with colleagues at Stanford, who will conduct advanced “multiomics” analyses, meaning they will bring together data on genes, cellular proteins and much more to obtain a more holistic understanding of exercise’s benefits to the body.

UVA’s research team includes Yan, of the Robert M. Berne Cardiovascular Research Center and the Departments of Medicine, Pharmacology and Molecular Physiology and Biological Physics; Wenhao Xu, PhD, of the Department of Microbiology, Immunology and Cancer Biology; Chongzhi Zang, PhD, of UVA’s Center for Public Health Genomics, the Department of Public Health Sciences and the Department of Biochemistry and Molecular Genetics; Matthew Wolf, MD, PhD, of the Department of Medicine’s Division of Cardiovascular Medicine and the Robert M. Berne Cardiovascular Research Center; Thurl Harris, PhD, of the Department of Pharmacology; and Alban Gaultier, PhD, and John Lukens, PhD, both part of UVA’s Department of Neuroscience and the Center for Brain Immunology and Glia (BIG).

“It is well known that exercise is one of the best treatments for mood disorders,” Gaultier said. “We are excited to test the group discoveries using animal models of anxiety and depression.”

“This is an exciting opportunity for team science,” Zang said. “I am happy to work with colleagues at UVA and across the country and use data-science approaches to unravel the complex molecular effects of exercise.”

UVA’s effort has received almost a half-million dollars in backing from the NIH’s fund for MoTrPAC’s research.

“Our research team encompasses exceptional talents. The collective wisdom and expertise of the team at UVA and MoTrPAC will allow us to reach a level that we would not be able to reach by an individual,” Yan said. “It is an unprecedented opportunity in our lifetime to tackle this incredibly important question to mankind.”

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

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