Wake Forest University School of Medicine Research Roundup

Recently published findings and publications from our faculty

December 13, 2023

Study Finds Differences in Time Perception Consistent with Varying Clinical Symptoms of Parkinson’s Disease


WINSTON-SALEM, N.C. – Dec. 13, 2023 – Scientists from Wake Forest University School of Medicine have shown that the way patients with Parkinson’s disease perceive time may be indicative of underlying conditions that are known to be dopamine-dependent.

“For example, we could predict whether a patient had a behavioral addiction disorder or depression simply based on how they experienced the passing of a few hundred milliseconds,” said Kenneth Kishida, Ph.D., associate professor of physiology and pharmacology at Wake Forest University School of Medicine and principal investigator.

For the study, the research team measured how patients with Parkinson’s disease perceived the passing of (very short) intervals of time. This process is thought to be affected by dopamine, a neurotransmitter that’s made in the brain and acts as a chemical messenger, communicating between nerve cells in the brain and the rest of the body.

The study findings were recently published in Parkinsonism & Related Disorders.

“One potential impact of this work is the possible development of a behavioral biomarker that could augment diagnosis and treatment strategies for patients in neurology, psychiatry and those receiving deep-brain stimulation in neurosurgery,” Kishida said.

The study team is also conducting additional research to monitor subsecond fluctuations in dopamine in patients with these same conditions to gain insight into the mechanisms that dopamine influences and how these mechanisms are altered in patients with depression, addiction disorders and dopaminergic movement disorders.

The study was supported by grants from the National Institutes of Health: KL2TR00142, R01DA048096, R01MH121099, R01NS092701 and R01MH124115, and a Biotechnology and Biological Sciences Research Council grant: BBR01583X1.


Preclinical Study Suggests Bacterial Components Inside Abdominal Fat

– Not the Amount of Fat – Impact Health


WINSTON-SALEM, N.C. – Dec. 13, 2023 –A new preclinical study from scientists atWake Forest University School of Medicineis shedding light on the bacterial components inside abdominal fat and their impact on health.


The study was recently published in Obesity.


Cardiovascular disease is the leading cause of death and disability. Risk for cardiovascular disease is driven by diabetes, high blood pressure and unhealthy blood cholesterol levels, which are all often seen in people who are overweight or obese. However, this cluster of risk factors, known as metabolic syndrome, also occurs in thin people while many overweight people are also very healthy.


“More than 10% of lean individuals also have metabolic syndrome,” said Kylie Kavanagh, D.V.M., professor of pathology and comparative medicine at Wake Forest University School of Medicine and corresponding author of the study.  “And 30% of individuals with obesity do not meet the metabolic syndrome criteria, so there are other factors to consider.”


One consideration in need of evaluation is the bacteria within our intestines, on our skin and in our tissues.


For the study, the research team analyzed the bacteria of visceral adipose tissue, which is the fat tissue deep inside the abdomen, in nonhuman primates (NHP) with varying metabolic statuses.


“In unhealthy lean and obese NHP models, we found that the microbiome was enriched withmore gram-negative bacterium,” Kavanagh said.


According to Kavanagh, gram-negative bacteria tend to be more pathogenic and incite more inflammation where they are detected.


The researchers discovered that the bacteria populated the fat tissue and were unrelated to weight. Further, the immune systems in the unhealthy models were less able to calm the local inflammation induced by this bacterium.


“This research highlights pathways for potential treatment of metabolically unhealthy people with or without obesity,” Kavanagh said.


The study was supported with grants from the National Heart, Lung and Blood Institute, R01HL142930, and the National Institutes of Health, ULTR001420.


Study Shows New Approach in Maintaining Islet Health


WINSTON-SALEM, N.C. – Dec. 13, 2023 Islets are clusters of cells in the pancreas that detect blood glucose and produce insulin. The use of pancreatic islet transplantation to provide a replacement for the lost insulin-producing cells has proven to be a valuable therapy for treating Type 1 diabetes, but it is effective only for a short time. A major reason behind this failure is that islets do not do well once they are removed from their natural environment. 

But now a study from scientists at Wake Forest University School of Medicine shows a new approach to maintaining islet health in a laboratory setting, which is significant for islet transplantation.

The study was recently published in Acta Biomaterialia.

“I believe this is the first study to show the importance of the extracellular matrix (ECM) in maintaining islet health long term” said Amish Asthana, Ph.D., assistant professor of surgery at Wake Forest University School of Medicine and co-principal investigator of the study.

The ECM is a large network of proteins and other molecules that surround, support and give structure to cells and tissues in the body.

For the study, the researchers sought to increase the lifespan and function of islets by recreating the islet’s natural environment, using an organ decellularization technology.

Current decellularization methods use harsh detergent-based solutions that disrupt the fibrous nature of the ECM. They also remove many critical signaling molecules present in the ECM like growth factors and cytokines, thereby reducing its potency. However, the team recently developed a novel, non-detergent-based decellularization method that preserves the molecular integrity and molecular factors.

Using the gentler decellularization process, scientists observed improved islet function.

“The knowledge from this study can lead to advancements in the field of pancreatic tissue engineering,” said Giuseppe Orlando, M.D., Ph.D., an associate professor of surgery at Wake Forest University School of Medicine, a transplant surgeon at Atrium Health Wake Forest Baptist and principal investigator of the study. 

The authors said the findings are significant because the banking of healthy islets could potentially revolutionize clinical islet transplantation. Maintaining long-term islet function can also potentially result in the development of long-term models to study the pathophysiology of the disease and test potential treatments.

The study was supported by grants from the European Union's Horizon2020 research and innovation program No. 646272; the National Center for Advancing Translational Sciences; National Institutes of Health No. UL1TR001420, National Institute of Diabetes and Digestive and Kidney Diseases No. R01 DK116875 and the Diabetes Research Institute Foundation.

Conflict of Interest: Orlando is a board member for Seraxis Inc., a biotechnology company with an emphasis on islet replacement therapy. Orlando also has two patents pending related to the decellularization process and insulin-secreting cells. He also holds a patent related to organ and tissue decellularization.


Silver Nanoparticle-induced Photothermal Therapy Shows Promise in Treating Breast Cancer Cells


WINSTON-SALEM, N.C. – Dec. 13, 2023 – What impact do bacteria living inside breast cancer cells have on treatment response and outcomes?

It’s a question that researchers at Wake Forest University School of Medicine explored in a study recently published in Pharmaceutics.

“Breast cancer can harbor intracellular bacteria, which may have an impact on metastasis and therapeutic responses,” said Nicole Levi, Ph.D., associate professor of plastic and reconstructive surgery at Wake Forest University School of Medicine and the study’s corresponding author.

Silver nanoparticles are known for their antimicrobial activity, and they are FDA-approved for effectively killing a variety of cancer cells. Photothermal therapy is a relatively new cancer therapy that converts light into heat energy to kill cancer cells and bacteria.

“Cancer cells with bacteria inside of them can be resistant to traditional treatments, and the bacteria are difficult to kill when they reside inside,” Levi said. “So, our study looked at the impact of silver nanoparticle-induced photothermal therapy.”

The research team found that both tumorigenic and non-tumorigenic breast cells are resistant to heat or silver nanoparticles, when bacteria are present.

“Our findings demonstrate that the application of brief photothermal heating of cells using silver nanoparticles offers a synergistic benefit in killing both infected and non-infected cells,” Levi said.

Additional research is needed to evaluate how reducing intracellular bacteria can improve responses to breast cancer treatments such as chemotherapy.


Non-Hispanic Black Children Receive Pharmacologic Restraint More Often Than Other Racial Groups


WINSTON-SALEM, N.C. – Dec. 13, 2023 – A new study shows that among children hospitalized for mental health crises, non-Hispanic Black children were at the highest odds of pharmacologic restraint compared to other racial/ethnic groups.

The study findings were recently published in Pediatrics.

“Children in mental health crises are increasingly admitted to children’s hospitals to wait for inpatient psychiatric placement,” said Ryan Wolf, M.D., assistant professor of pediatrics at Wake Forest University School of Medicine. “During their stay, behavioral problems and acute agitation may occur.”

Pharmacologic restraint involves the administration of medications for acute agitation.

For the study, researchers conducted a retrospective study of children admitted for a primary mental health condition from 2018-2022 at 41 children’s hospitals in the U.S. and analyzed 61,503 hospitalizations.

Pharmacologic restraint was used in 7,309 hospitalizations or 11.9%. Non-Hispanic White children represented 54.8% of the group compared to 19.8% non-Hispanic Black children. Non-Hispanic Black children had the highest use of pharmacological restraint (14.8%) among all racial/ethnic groups.

“These findings indicate the urgent need for implicit bias training and de-escalation training,” Wolf said. “It’s crucial that health care systems and providers address these disparities in mental health care.”

Wolf conducted this research at Monroe Carell Jr. Children’s Hospital at Vanderbilt.