Author: yec14002

UConn Dental Alumna Gives Back

Dr. Carolina Giraldo


UConn School of Dental Medicine alumna Dr. Carolina Giraldo ’95 has always persevered.

Born in Bogotá, Colombia, and raised in Bridgeport, Connecticut, Giraldo and her older sister took care of themselves and their younger brother from an early age while their parents worked three jobs. Giraldo knew she’d have to work hard to be successful, juggling work and study to put herself through college and then dental school.

Now she’s paying it forward. Giraldo, who opened her own dental practice soon after earning her doctorate, recently made a $1 million planned gift to help students like herself. Giraldo established the Dr. Carolina Giraldo Scholarship in 2017 so dental students from underrepresented groups might have an easier time becoming dentists than she did.

“I want the minority population to grow in the field,” Giraldo says. “I want a bigger presence of women, of minorities, to get into the field and make a difference.”

Dr. Sarita Arteaga, the dental school’s associate dean for students, says scholarships like Giraldo’s help students with “the little things,” not just tuition.

“It also helps them to know that someone is investing in them,” she says. “They say, ‘Wow, I can’t believe somebody was in this position and not only wants to give back to the school, but wants to do the same thing for me.’”

To support the Dr. Carolina Giraldo Scholarship Fund, visit s.uconn.edu/giraldo.

UConn, JAX Confront Pain With First-In-State Consortium

illustration of older man holding back in pain


An estimated 100 million Americans suffer from chronic pain — more than those affected by heart disease, cancer, and diabetes combined, according to The National Academies of Science, Engineering, and Medicine. How best to manage that pain in the face of a nationwide opioid crisis is the question on many practitioners’ minds.

The Connecticut Pain Consortium — a translational pain research and education collaboration between UConn Health, the UConn schools of Medicine and Nursing, and The Jackson Laboratory — aims to help answer it.

Given the broad range of research interests and funding opportunities related to pain, the founders envision that centers across the University and nearly every UConn school and college — particularly the schools of Dental Medicine and Pharmacy — will join the consortium to build mutually beneficial collaborations. Experts from Yale University and hospitals including Connecticut Children’s Medical Center will also be involved.

“There is a clear need for more basic and translational research on human pain and pain management,” says the Consortium’s director, mathematician and computational biologist Reinhard Laubenbacher, a joint faculty member at UConn Health and The Jackson Laboratory for Genomic Medicine.

“And there is a critical unmet need for education and training of providers and patients. This is a great opportunity to deploy our capabilities in pain research and addiction together with our Connecticut partners in an exciting and much-needed statewide initiative.”

The Consortium, the first of its kind in the Connecticut medical community, will establish a portal for pain-related health care data and facilitate research collaborations that leverage state and national resources. It will aim to translate that research into cutting-edge pain management solutions and raise awareness of the many facets of pain, pain management, and potential related ramifications including opioid addiction. The Consortium will contribute to a curriculum on pain research and management for health care providers.

The launch is being funded by a $55,000 planning grant from the Mayday Fund, whose mission is to support projects that close the gap between knowledge and practice in the treatment of pain, to the UConn Foundation. The Consortium has also received support from the UConn Office of the Vice President for Research, the schools of Nursing and Medicine, and the Jackson Laboratory for Genomic Medicine.

“This new consortium builds upon strengths already existing in the School of Medicine, with an existing core of faculty focused on pain research,” says Dr. Bruce T. Liang, dean of the School. “Thanks to this grant, we believe there will be numerous opportunities for advancement in the study and treatment of pain.”

Honor Roll – Fall2018

Wizdom Powell, Ph.D., director of the UConn Health Disparities Institute, was named to the National Advisory Committee for the Robert Wood Johnson Foundation’s Interdisciplinary Research Leaders program.


UConn medical student Tiahna Spencer is one of 34 medical students in the U.S. chosen for the National Institutes of Health Medical Research Scholars Program 2018–19 class.


Dr. Bruce T. Liang, dean of UConn’s medical school, was recognized by The Asian Pacific American Coalition of Connecticut (APAC-CT) at its 2018 gala for his significant contributions to the welfare of the state’s Asian Pacific American community.


Dr. R. Lamont “Monty” MacNeil, recently retired dean of the UConn School of Dental Medicine, received The Fones Medal, the top award from the Connecticut State Dental Association (CSDA), at its annual meeting for his outstanding contributions and dedication to the CSDA and the profession of dentistry.


Paramedic Peter Canning, UConn Health’s emergency medical services (EMS) coordinator, received the Connecticut Department of Public Health Commissioner’s Award at the DPH’s 2018 EMS awards ceremony.


Dr. Rajesh V. Lalla is the new president of the Multinational Association of Supportive Care in Cancer. He will serve a two-year term.


Dr. Marja Hurley has been selected as a Fellow of the American Society for Bone and Mineral Research (ASBMR) Advisory Committee.


Dr. Cato T. Laurencin has been selected by The American Ceramic Society to present the Edward Orton Jr. Memorial Lecture at the 14th annual Materials Science and Technology meeting.

Together for the Kids

By Lauren Woods

Dr. Emily  Germain-Lee  with a patient at the Albright Center at Connecticut Children's Medical Center.

Dr. Emily Germain-Lee with a patient at the Albright Center at Connecticut Children’s Medical Center.
Erin Blinn Curran/ Connecticut Children’s Medical Center


National recognition by external sources such as U.S. News & World Report comes as no surprise to the thousands who pass through Connecticut Children’s Medical Center each year.

What may be unexpected to those patients is that such success is the fruit of a more than 50-year legacy of the pediatric department at UConn School of Medicine advancing pediatric medicine, research, and education in Connecticut — and putting the health of the state’s tiniest residents first.

The life-changing work done by UConn’s Department of Pediatrics is made possible by a special partnership: Connecticut Children’s Medical Center is the teaching hospital where medical students, pediatric residents, and fellows are trained, as well as the home of the faculty’s clinical care work.

“UConn’s Department of Pediatrics’ strong relationship with Connecticut Children’s is excellent and seamless. There is no us and them. We are truly one, and we couldn’t excel without each other,” says Dr. Bruce T. Liang, the dean of the UConn School of Medicine since 2015. Liang has helped expand the two institutions’ joint recruitment of world-renowned physician-scientists and has led much of their growth in pediatric research.

For the Greater Good

The seeds of excellence in pediatric care in the Hartford area were planted in 1967 with the founding of UConn’s Department of Pediatrics, shortly before the medical school admitted its first class in 1968. UConn John Dempsey Hospital offered pediatric hospital care when it opened in 1975. Hartford-area hospitals had an informal agreement not to duplicate pediatric specialty services — patients were transferred among the hospitals based on their specialty care needs.

Connecticut Children’s was born in April 1996 after Newington Children’s Hospital, Hartford Hospital, and John Dempsey voluntarily closed their pediatric services so a comprehensive children’s hospital could open. It was established by state legislation and a 99-year lease of land on Hartford Hospital’s campus for 1 dollar per year. St. Francis Hospital and Medical Center’s pediatric programs were also incorporated. Uniquely, the leadership structure of the new pediatric hospital required that the same individual serve as both UConn’s Department of Pediatrics chair and Connecticut Children’s physician-in-chief.

“I am honored to have seen firsthand the strong evolution in pediatrics since my 1980s UConn pediatric residency training,” says Dr. Juan C. Salazar, who has served in that joint leadership role at UConn and Connecticut Children’s since 2013. “It is amazing that the strengths of four different Hartford hospitals came together for the greater good of our children and continue to offer the best pediatric care. It’s been an incredible success, allowing us to grow pediatrics clinically and educationally, along with our research mission.”

Salazar cites pediatric endocrinologists Dr. David Weinstein and Dr. Emily Germain-Lee as “two of several perfect examples of how the partnership of Connecticut Children’s and UConn really works seamlessly, with clinical services provided at Connecticut Children’s while robust laboratory research and clinical trials are under way at UConn.”

For 2018–19, U.S. News & World Report ranks Connecticut Children’s among the best hospitals in four pediatric specialties: cardiology and heart surgery, diabetes and endocrinology, neonatology, and urology. As one of the state’s largest care providers with 300 faculty members, UConn’s Department of Pediatrics has 31 medical and 13 surgical specialties.


Dr. David Weinstein, head of the Glycogen Storage Disease Program at UConn Health and Connecticut Children’s Medical Center, walks with Alyssa Temkin through the new clinic at Connecticut Children’s.

Dr. David Weinstein with a patient
Peter Morenus


For a Brighter Future

In addition to translational research and top clinical care, UConn Health’s mission includes a third focus on teaching the practitioners of tomorrow. UConn is the largest educator for the state’s pediatric medicine workforce, as up to 60 percent of pediatricians in Connecticut have graduated from UConn’s medical school or its pediatric training programs.

Historically, UConn has also provided the largest pipeline of medical students into the state’s pediatric residency programs — each year up to 20 percent of UConn’s graduating medical school class chooses to specialize in pediatrics, entering residency training programs here or around the country.

“Along with research advancements, our significant focus is the education and training of our next generation of pediatricians and pediatric specialists, many of whom stay right here in Connecticut to serve the state,” says Liang.

UConn and Connecticut Children’s continue to strengthen their partnership in all three areas by building relationships with other organizations.

The two institutions in 2016 joined with another collaborator, The Jackson Laboratory (JAX) for Genomic Medicine located on UConn Health’s campus, to recruit Dr. Ching C. Lau, an internationally recognized pediatric brain and bone tumor clinician and researcher.

UConn and Connecticut Children’s look forward to growing their alliance, Liang says, and are planning joint physician-scientist recruitments in the fields of medical genetics and gastroenterology, as well as further collaborations in maternal-fetal medicine.


arrow

World-renowned physician-scientists across specialties bring to life the vision of Connecticut Children’s Medical Center and UConn School of Medicine’s Department of Pediatrics. Read on to learn about three of the groundbreaking physician-scientists who are currently dedicated to improving the lives of children in Connecticut and around the world.


A Vision for the Future of Pediatric Cancer

In 2016, Connecticut Children’s and UConn joined with another collaborator, The Jackson Laboratory (JAX) for Genomic Medicine located on UConn Health’s campus, to recruit Dr. Ching C. Lau, an internationally recognized pediatric brain and bone tumor clinician and researcher, from Texas Children’s Hospital in Houston.

As medical director of hematology-oncology at Connecticut Children’s and head of the Division of Pediatric Hematology-Oncology in the Department of Pediatrics at UConn, Lau’s JAX-based laboratory aims to leverage new, sophisticated genomic medicine techniques, mouse models, and therapeutic treatments to choose the best therapy for patients and discover new treatments.

When he was awarded the inaugural Martin J. Gavin Endowed Chair in Hematology/Oncology at Connecticut Children’s, Lau said he was attracted to the vision and dedication of Connecticut Children’s Medical Center.

“I dream that one day when I look at a child diagnosed with cancer, I can look him or her in the eye and say, ‘You will be cured without having to come to the hospital for therapy. You just have to go home and take this medicine,’” he said.

Lau is focused on accelerating the pace and success rate of clinical trials in pediatric cancer patients. “Although the incidence of cancer among children is much lower than that in adults,” he says, “it can be just as deadly. And because of the smaller number of patients available, clinical trials of new treatments for pediatric cancers are conducted at a much slower pace. Typically patients are enrolled in clinical trials after their cancers progress or are found not to be responsive to standard therapy.”
As a result, he says, pediatric cancer patients are exposed to side effects of standard therapy without therapeutic benefit. “This is a particularly serious problem for children because they are still undergoing normal growth and are particularly vulnerable to the side effects of anticancer drugs.”

By using the combined approach of genomic medicine and accurate mouse models to choose the best therapy for each patient, Lau hopes to improve the speed and outcome of clinical trials as well as to reduce unnecessary side effects for children with cancer.

One way he’s speeding up the process is through Smash Childhood Cancer, an initiative he’s spearheading for the U.S. alongside international researchers and IBM to find prospective treatments for childhood cancers by conducting millions of virtual experiments to help pinpoint promising drug candidates for further study using IBM’s World Community Grid.

“This kind of research expedites finding new treatments for childhood cancers,” Lau says. “Crowdsourcing computer processing power enables us to perform millions of experiments virtually and will save us years of experiments. It is bringing us that much closer to finding the right drug for each type of cancer.”

 

Administering New Therapy — and Hope

In late July, a patient named Jerrod received a drug infusion that he’s been waiting for his entire life.

Jerrod was the first patient to receive a promising investigational gene therapy to treat glycogen storage disease type Ia, the rare, potentially deadly genetic disorder he was born with. Dr. David Weinstein, a world-renowned pediatric endocrinologist and director of the Glycogen Storage Disease Program at Connecticut Children’s Medical Center and UConn Health, has been working to develop the treatment for two decades and calls the trial “a big leap forward for GSD.”

Healthy livers store excess sugar from food and release it into our bloodstreams when we need it as processed sugar enzymes called glycogen. However, in the seven forms of GSD, the liver fails to break down glycogen into glucose, causing the body’s blood sugar levels to drop dangerously low, which can lead to seizure or death. Patients stay alive by consuming a cornstarch mixture every few hours to keep their blood sugar up.

The gene therapy undergoing the Phase 1/2 clinical trial, approved by the FDA in April, delivers a new copy of the gene to the patient’s liver to replace deficient sugar enzymes and jumpstart the body’s glucose control. Studies in animal models have already shown the promising gene therapy to be safe, effective, and long-lasting.

The clinical trial is in conjunction with the biopharmaceutical company Ultragenyx and will soon expand from UConn Health in the U.S. to other sites including Canada, Spain, and the Netherlands.

“This gene therapy is hope for all us GSD patients,” says Jerrod, who asked that his last name be withheld. “We are all extremely excited. Dr. Weinstein is a savior and so is the entire GSD program.”

Weinstein moved his GSD program — the largest in the world — to Connecticut Children’s and UConn Health in early 2017. His multidisciplinary team cares for 600 patients from 48 countries.

“The strong synergies and collaborative team science happening at UConn and Connecticut Children’s are world class and the most fertile ground to make a GSD cure reality,” says Weinstein.

 

Writing the Rulebook

Dr. Emily Germain-Lee, a professor of pediatrics and chief of pediatric endocrinology and diabetes, moved her first-of-its-kind Albright Center from Johns Hopkins School of Medicine and Kennedy Krieger Institute to UConn and Connecticut Children’s in October 2016. She has cared for more patients who have a specific rare set of endocrine diseases than any other doctor in the world.

“She has redefined the field of pediatric endocrinology,” Salazar said when the hire was announced. “Patients and families travel from all over the world seeking Dr. Germain-Lee’s care.”

Germain-Lee’s patients suffer from pseudohypoparathyroidism and its related disorders, including Albright hereditary osteodystrophy (AHO), a rare inherited bone disorder caused by a genetic mutation that often leads to short bones and short stature. It is also frequently accompanied by severe multihormonal dysfunction in the body.

This summer, Germain-Lee co-authored the first international guidelines to help doctors around the globe diagnose and manage patients with the diseases. The new guidelines call for human growth hormone treatment for the vast majority of the patients who are at risk for short stature due to growth hormone deficiency. Germain-Lee was the first to discover that part of the reason why AHO patients are short is that two-thirds of them have a growth hormone deficiency.

Her long-term global clinical trial studies have shown the promising benefits of growth hormone treatment, including its ability to drastically increase a patient’s short stature to their original destined height potential while also improving their lipid levels and reducing obesity. With her research in the final stages, Germain-Lee is working toward gaining FDA approval of the therapy, which would be the first new therapy for the disorder in 70 years.

“I am thrilled to be a part of the combined power of UConn School of Medicine and Connecticut Children’s Medical Center for advancing children’s health and discovering new treatments of disease through research,” says Germain-Lee.

Curators Versus Cancer

By Kim Krieger | Illustrations by Kailey Whitman

illustration of scientist look over hundreds of books

A special team of medical literature experts are on the hunt for cancer’s kryptonite, one mutation at a time.


If the genetic code is like a book, then a mutation is like a typo. Some typos are meaningless. Others have such dramatic consequences for a book, or a life, that the error alone could have an entire novel written about it.

Cancer mutations are like that. As oncology moves toward precision medicine — the idea that if we knew exactly which genetic mutations make a particular cancer tick, we could pick exactly the right treatments — oncologists have to keep up with an ever-expanding library of mutations and the drugs that might foil them. The number of cancer research papers published increases every year; there were about 35,000 published in 2015 just in the U.S. It’s far more than any one person can keep up with.

In the same way that a university has research librarians who keep up with the literature in specific fields, JAX has experts who keep up with cancer gene and drug research, even studies that are ongoing and not yet published.

A new collaboration between UConn Health and The Jackson Laboratory (JAX) hopes to help oncologists find the right treatments by keeping up with research for them — and using the institutions’ combined expertise in cancer treatment, molecular biology, and genetics to improve patient outcomes for cancers that currently don’t have good treatments. In the same way that a university has research librarians who keep up with the literature in specific fields, JAX has experts who keep up with cancer gene and drug research, even studies that are ongoing and not yet published. JAX already successfully connects these experts with doctors in the Maine Cancer Genomics Initiative, a philanthropy-funded statewide precision medicine program. UConn Health and JAX hope to expand the concept and demonstrate its feasibility more widely.

A UConn Health researcher holds a tumor sample.

A UConn Health researcher holds a tumor sample. Kristin Wallace

Bull’s Eye Treatment

Imagine that a patient has surgery or a needle biopsy to diagnose a tumor. It’s a particularly ugly tumor, the surgeon, oncologist, and pathologist all agree. Invasive, spreading, and perhaps this isn’t the first time this patient has had to come in for cancer surgery. The tumor is sampled and sent for genetic testing. In about two weeks, the results come back: there are three genetic variants in the tumor that might be drug targets.

At UConn Health, oncologists can send portions of particularly malignant tumors to a team at the JAX Clinical Laboratory. JAX sends back a report with information the oncologist can use to pick a drug regimen with the best chance to shrink that ugly tumor. “The goal is to define the optimal treatment regimen for each individual patient” who may not have good options otherwise, says Dr. Ketan R. Bulsara, chief of neurosurgery at UConn Health and one of the principal investigators on the project.

At UConn Health, oncologists can send portions of particularly malignant tumors to a team at the JAX Clinical Laboratory. JAX sends back a report with information the oncologist can use to pick a drug regimen with the best chance to shrink that ugly tumor.

The report is intended to be a standalone reference an oncologist can use to inform a treatment plan. But if the oncologist is unfamiliar with one of the mutations identified in the report or just wants more information, they can request that a genomic tumor board be convened. The board is composed of surgeons, pathologists, and molecular oncologists who act as external advisors, sharing their opinions with the oncologist. In just 15 minutes, the oncologist can get a wealth of expert opinion to combine with their own expertise and judgment. In the end, the oncologist and patient decide on the best treatment, based on all the available information.

“In a multidisciplinary fashion, doctors and scientists work hand in hand in this with one common goal: identify the best treatment regimen for that particular patient’s pathology,” Bulsara says.
The focus is always on the patient. But behind the scenes, there’s an entire team of researchers whose work goes into the genetic tumor report. Scientists at JAX Clinical Laboratory sequence the tumor’s genetic code and report information on more than 200 cancer-related genes. The genes were picked because they are associated with both malignancy and potential drug treatments. Any mutations or variants in these genes might be a clue to the cancer’s weakness. Or a red herring.

“A typical tumor might have 2,000 mutations. Not all of them really matter,” says Andrey Antov, the program director for the Maine Cancer Genome Initiative at JAX. Finding the key mutations that matter, the two or ten or twenty that could possibly inform treatment and a better outcome for the patient, is the job of the clinical genomic curators.

Personal Librarians

The clinical genomic curators are specialists in fields such as molecular oncology and oncological pharmacology. They’re dedicated to keeping up with the literature on cancer genes and the drugs that target them. More and more of these drug-gene connections are being discovered every day. It’s exciting, but the sheer volume of papers can be overwhelming. Navigating that ocean of scientific papers is the medical curators’ full-time job. They’re like librarians curating a Boston Public Library–size collection of genes and drugs with no cross references in the card catalog and only an imperfect search function. The hope is that just as a good librarian’s knowledge of the subject matter can unearth texts a researcher would never otherwise find, a medical curator’s grasp of oncological genetics and pharmacology can identify potential treatments that would otherwise remain obscure.

Each mutation identified by the genetic panel might require 10 to 20 scientific publications to understand. Once the curators have a handle on the variants’ significance, the clinical laboratory decides which two or three should be described in the report to the oncologist.

illustration of books in a library cart

Sifting the information down to something relevant and digestible is the ultimate goal.

“Today, all this information is disorganized and may not all be in the oncologist’s head. We’re trying to bring it together,” says Jens Rueter, medical director for the Maine Cancer Genome Initiative.

The ideal outcome of a tumor genetic analysis would be to identify a mutation such as the HER2 gene that is turned on in the most aggressive breast cancers. HER2 is responsible for the cancer’s malignancy. But it’s also the cancer’s Achilles’ heel. Once drugs were developed to block the HER2 protein, survival rates climbed sharply.

The goal of the Maine Cancer Genomics Initiative is to enable oncologists to identify other drug-gene connections as potent as the ones found for HER2. Although more and more of these drug-gene connections are being discovered, it remains difficult to provide a patient with access to these drugs. Many of them are only available if a patient participates in a clinical trial. And often, there are barriers to accessing clinical trials, and getting drugs off-label is the only way to get patients to treatments. That’s another benefit that Antov, Bulsara, and Rueter hope UConn Health’s collaboration with JAX will bring.

Positive Outcomes

Ultimately, the researchers hope to demonstrate that this approach leads to better outcomes for patients. During the past year more than 350 patients and 70 oncology practitioners (more than 80 percent of the Maine oncology community) enrolled in the Maine Cancer Genomics Initiative study protocol. A few patients have already been offered a targeted treatment through a trial or a compassionate drug access program as a result of enrollment in the program. And Maine health care professionals have logged more than 1,200 certified education hours through 35 genomic tumor boards, online modules, and annual forums held by JAX.

So far, five patients have done this at UConn Health within the last two months. Generous donors have given enough to fund 20 more.

The hope is that just as a good librarian’s knowledge of the subject matter can unearth texts a researcher would never otherwise find, a medical curator’s grasp of oncological genetics and pharmacology can identify potential treatments that would otherwise remain obscure.

“We hope to get funding for at least 100 patients to show the feasibility of this approach,” Bulsara says. “We want to show we can do this reliably, and that it reliably improves patient care.”

UConn Health already has the infrastructure to do this, in particular a biorepository for tumors set up by Neag Cancer Center Director Dr. Pramod Srivastava and pathologist Dr. Melinda Sanders. With that foundation and support from UConn medical school Dean Dr. Bruce Liang and UConn Health CEO Dr. Andrew Agwunobi, the program was piloted in the Department of Surgery by Bulsara, its chief of neurosurgery, with support from Department of Surgery Chairman Dr. David McFadden, hematology and oncology chief Dr. Susan Tannenbaum, anatomical pathology chief Dr. Qian Wu, and JAX Clinical Laboratory Director Honey Reddi.

If the UConn Health–JAX initiative does prove its feasibility, the approach will continue to spread and become a standard of care.

More oncologists could have access to the library of knowledge and advice of a genetic tumor board, and more cancer patients could benefit from longer, healthier lives.

Tumor samples are housed in UConn Health's research biorepository.

Tumor samples are housed in UConn Health’s research biorepository. Kristin Wallace

Follow-Up – Fall 2018

Research doesn’t stop when we report it. Here is an update on a past UConn Health Journal stories:


Glycogen Storage Disease

Dr. Annabelle Rodriguez-Oquendo, professor of cell biology at the UConn School of Medicine, was recently issued a diagnostic patent to test for a genetic predisposition for an abnormal inflammatory response that causes several life-threatening disorders, like coronary artery disease and chronic inflammatory disease. Lipid Genomics, the start-up Rodriguez-Oquendo founded in 2010, has exclusively licensed the technology from UConn Health. The company is currently in discussion with potential investors to continue commercialization of this product, as well as other therapeutic innovations for HDL-cholesterol dysfunction.

Winter 2015, “Getting to the Heart of the Matter”

Better Ways to Heal Bones

Julie Bartucca

illustration of engineers going over blueprint of human skeleton with engineering notes on the hip bones

UConn Health is engineering innovative solutions for bone and joint problems, promoting faster recovery and less trauma to the body.


We’ve all signed a child’s colorful cast on their broken arm, gotten a call to inform us an elderly relative fell and broke a hip, or been laid up with back spasms ourselves. Maybe you’ve had a knee replacement or dealt with joint pain from years of athletic activity. It’s practically inescapable — 1 in 2 American adults suffers from a musculoskeletal disorder or injury such as arthritis, chronic back pain, fractures, or osteoporosis, according to 2016 data from the United States Bone and Joint Initiative (USBJI).

This is compounded by the fact that the U.S. has a rapidly aging population and, as people age, they lose bone density and the risks increase. Experts say the incidence of and costs to treat such issues are in danger of spiraling out of control.

But researchers at UConn and UConn Health are using a host of materials and technologies — from stem cells to spider-spun silk fibers to hydrogel to ultrasound waves — to strengthen bones and joints and accelerate recovery from musculoskeletal diseases and injuries.

“Musculoskeletal injuries are among the most common reasons to see a doctor. If we can take care of those faster and more effectively, patients can get back to their activities and work faster.”

“Musculoskeletal injuries are among the most common reasons to see a doctor. If we can take care of those faster and more effectively, patients can get back to their activities and work faster, which helps everybody,” says Dr. Augustus D. Mazzocca, director of the UConn Musculoskeletal Institute (MSI) and chair of the Department of Orthopaedic Surgery at UConn Health.

“There’s the economic impact of having people out of work, and the emotional problems of people who lose mobility and are isolated,” he says. “We’re trying to bring you back into society and get you back to what you like to do.”

To that end, UConn Health doctors also are developing ways to get you home faster after any musculoskeletal procedure, including spearheading same-day joint replacements.

Faster, Safer Recovery

UConn Health hip and knee replacement patients don’t have to wait for our clinical innovations to come to market. They can benefit from new approaches to the surgeries right now — and “right now” might also describe when they can go home post-op.

“Nearly 100 percent of my patients go home within 24 hours, and some now the same day,” says Dr. Mo Halawi, a new UConn Health orthopaedic surgeon who specializes in joint reconstruction and is spearheading an effort to minimize the time these patients spend in the hospital recuperating.

“The criteria for discharge are identical whether a patient leaves on the day of surgery or several days later. But with minimally invasive techniques, regional anesthesia, blood-conserving strategies, opioid-sparing analgesia, and immediate mobilization, patients are now achieving recovery milestones a lot quicker than before,” he says.

According to Halawi, the ideal candidate for same-day total joint replacement is one who is independent, motivated, has a good support system, and has no major risk factors for surgical complications. Much of the work is done in advance to optimize patients’ health and prepare them for surgery, allowing for the
speedy discharge.

After surgery, Halawi takes a less-is-more approach. Patients get on their feet right away and have no IV medications, drains, catheters, dressing changes, braces, or laboratory tests. Very rarely do his patients get discharged to nursing homes or rehabilitation facilities. Studies have shown that “patients recover better and have fewer complications in the comfort
of their homes,” he says.

“Hip- and knee-replacement surgery is constantly evolving, and we need to always deliver safe, effective, efficient, and evidence-based medicine to our patients. Soon, more surgeons and patients will realize that long hospital stays and recovery times are outdated,” Halawi says.

Engineering Cartilage

Though it is in the very early stages of development, UConn Health tissue engineer Syam Nukavarapu and his team have created a hybrid hydrogel system that they hope is the first step toward forming a hypertrophic cartilage template with all the right ingredients to initiate bone tissue formation, vascularization, remodeling, and ultimately the establishment of functional bone marrow to repair long bone defects.

How the more than 200 bones in an adult human skeleton form and how they are repaired if injured varies and has posed a challenge for many researchers in the field of regenerative medicine.

The cartilage template Nukavarapu and his team created appears to overcome hurdles that make it difficult for regenerative scientists to help the body’s long bones regenerate.

Two processes involved with human skeletal development help all the bones in our body form and grow. These processes are called intramembranous and endochondral ossification: IO and EO respectively.

While they are both critical, IO is the process responsible for the formation of flat bones, and EO is the process that forms long bones like femurs and humeri.

For both processes, generic mesenchymal stem cells (MSCs) are needed to trigger the growth of new bone. Despite this similarity, IO is significantly easier to re-create in the lab since MSCs can directly differentiate, or become specialized, into bone-forming cells without any additional steps.

However, this relative simplicity comes with limitations. To circumvent the issues associated with IO, Nukavarapu’s team set out to develop an engineered extracellular matrix that uses hydrogels to guide and support the formation of bone through EO.

“Thus far, very few studies have been focused on matrix designs for endochondral ossification to regenerate and repair long bone,” says Nukavarapu, who holds joint appointments in the departments of Biomedical Engineering and Materials Science and Engineering. “By developing a hybrid hydrogel combination, we were able to form an engineered extracellular matrix that could support cartilage-template formation.”

Nukavarapu’s team’s findings could be the first step to initiating the proper healing of long bones with biomedical help.

Using the Wisdom of Spider Webs

When someone breaks a load-bearing bone — the femur, for instance — doctors might install a metal plate to support the bone as it fuses and heals. But the metal can cause inflammation and irritation, and since metals are very stiff, the new bone may grow back weaker and more vulnerable to fracture.

UConn materials scientist and biomedical engineer Mei Wei and her team have developed an alternative to metal: a composite made with silk fibroin, a protein found in the silk fibers spun by spiders and moths and a common component in medical sutures and tissue engineering because of its strength and biodegradability.

Wei’s study found that the high-performance biodegradable composite showed strength and flexibility characteristics that are among the highest ever recorded for similar bioresorbable materials.

Working with UConn mechanical engineer Dianyun Zhang, Wei’s lab created a mix of silk and polylactic acid fibers coated in bioceramic particles. The new composite lasts about a year — large, adult leg bones can take many months to heal — and then starts to degrade. No surgery is required for removal.


Tissue engineer Syam Nukavarapu (left) examines a specimen of his hybrid hydrogel in his UConn Health lab.


Capturing the Power of Ultrasound

In the Department of Orthopaedic Surgery and the Institute for Regenerative Engineering at the UConn School of Medicine, researchers Yusuf Khan, Bryan Huey, and Lakshmi Nair are studying the combined power of gel-encapsulated bone cells and ultrasound waves to help fractured bones heal.

Physical force has been shown to stimulate bone cell regeneration for full healing, but immobilizing the fracture with a cast doesn’t allow for any movement. Khan believes that adding cells to the fracture site early on, and then directing a transdermal physical force toward the cells via low-intensity ultrasound, could accelerate fracture repair. In cases where a fracture can’t heal on its own, the therapy could provide the necessary stimulus to complete the healing process.

The team’s lab has already demonstrated the successful placement of bone cell hydrogels in mice and is working with the Department of Materials Science and Engineering to optimize the gel capsules for human use.

Harnessing Stem and Amniotic Cell Strength

Dr. Cato T. Laurencin, the Albert and Wilda Van Dusen Distinguished Professor of Orthopaedic Surgery and the director of the Institute for Regenerative Engineering at UConn Health, is developing clinical therapies to treat — and potentially reverse the effects of — osteoarthritis using human amniotic tissue, stem cells, and new combinations of the two.

An estimated 20 percent of Americans suffer from osteoarthritis, the most common degenerative joint disease and the leading cause of disability worldwide. Although current surgical and non-surgical therapies can provide some relief, none treat the root cause of the disease.

Stem cells have been proven to reduce pain and improve function in osteoarthritis patients. New studies suggest that the use of stem cells may heal cartilage, but results vary. Thanks to the host of powerful cytokines contained in amniotic tissue, many of which have been shown to decrease inflammation, Laurencin believes human amniotic tissue may overcome the limitations of current stem cell therapies, providing an ideal delivery system with added benefits.

“Soon, more surgeons and patients will realize that long hospital stays and recovery times are outdated.”

In its initial studies, Laurencin’s team has found its amnion-based delivery system can support stem cell survival, growth, and proliferation, and that the combination of amnion matrices and stem cells have immunosuppressive and anti-inflammatory effects on knee tissue cells.

“We believe amniotic tissue growth factors help drive human development and regeneration,” says Laurencin. “We are hopeful that harnessing this powerful new cell combination will help us further advance regenerative engineering for patients, especially those with arthritis or sports injuries, who want to avoid steroid treatments or are interested in next-generation therapies.”

Although it is not yet covered by insurance, amnion tissue treatment is available now to Laurencin’s patients. Laurencin’s team hopes to make the combination amnion¬stem cell therapy available within the next three years.

From the advanced research that’s changing the care of the future to the clinical changes happening now, Musculoskeletal Institute head Mazzocca says the Institute is uniquely positioned to provide the best possible care to patients.

“We try to take all the clinical people that treat musculoskeletal disease — rheumatology, osteoporosis, comprehensive spine, orthopaedics — and put it in one place, and combine them with all the researchers so they can cross-pollinate and make care better for the people of the state of Connecticut,” he says. “And there’s nobody else in the state of Connecticut that does what we do.”

Jessica McBride, Colin Poitras, and Lauren Woods contributed to this story.

Unraveling

By Kim Krieger | Illustrations by Yesenia Carrero

illustration; two silhouettes, one with a scribble pattern overlayed over top. looks to scribbled circular dot between them

PTSD can undo a sufferer’s life. MDMA may help patients untangle their trauma and find their way back to mental health.


When lasting trauma is caused by callous acts of violence, the key to recovery can be making meaning from meaninglessness.

This year UConn Health will host a phase 3 FDA trial that tests whether the drug MDMA, known on the street as ecstasy or molly, is a safe and effective treatment for post-traumatic stress disorder. The disorder is difficult to treat, and many people have a tough time handling the treatment. MDMA not only might make therapy more tolerable but it also may help open a window for patients into their own mind. The insight allows them to process a shattering, horrific event into something that makes them stronger.

The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders defines post-traumatic stress disorder, or PTSD, as when a person is traumatized in some way and then continues to reexperience the trauma through flashbacks, nightmares, or unwanted intrusive memories. The person with PTSD avoids people or places associated with the trauma; becomes overly negative in thoughts and speech about themselves and other people; and has heightened arousal that can include a hair-trigger startle reflex, inability to sleep, hypervigilance, irritability, and aggression. At its worst, people are unable to cope with everyday life and may even become suicidal.

Often the source of the trauma is a shocking event involving interpersonal violence, such as rape, combat, or sexual abuse. Racial discrimination and harassment, particularly when it is shocking or pervasive, can also cause PTSD. UConn psychologist Monnica Williams began focusing on race-based trauma when she was at the University of Pennsylvania and had a very successful, high-achieving, black client come in with PTSD stemming from racial discrimination she’d suffered on the job. Williams was taken aback and began studying the link between racism and post-traumatic stress disorder.

Deconstructing the Trauma

But no matter what type of trauma causes the PTSD, the most effective treatment for it is exposure-based therapy, such as “prolonged exposure.” Essentially, the therapist has the patient discuss the traumatic event in excruciating detail, over and over again, until it ceases to cause overwhelming fear and anxiety.

Prolonged exposure works — indeed, it has the most evidence behind it. But it’s terribly difficult for the patients, who often get visibly upset during sessions, and many quit therapy because the experience is too much like the original trauma.

The MDMA-assisted therapy session was utterly without the distress, tension, and fear PTSD patients typically show during prolonged exposure treatment.

MDMA-assisted psychotherapy could be one way to change that. The drug stimulates the release of neurotransmitters that promote a feeling of trust and well-being and might also help the brain rewire itself. But when Williams first heard of it, she was skeptical.

“It sounded weird, like junk science, and I didn’t want to be part of that,” she says. But she agreed to take a look at an article in Psychopharmacology. She was fascinated to see that researchers had used MDMA as an adjunct to psychotherapy for PTSD and had gotten really good results. She was pleasantly surprised again when she first watched a video of an MDMA-assisted therapy session.

“People were sitting in a chair, relaxed. They’re processing it on their own, and would sometimes share new insights with the therapist,” Williams says. It was utterly unlike the distress, tension, and fear PTSD patients typically show during prolonged exposure. “They would say things like, ‘Wow. Now I understand the trauma didn’t happen to me because I’m a bad person — I was just in the wrong place at the wrong time.’ And we’re like, ‘Yes! Yes! They finally get it!’” she recalls. The MDMA helps them look at the big picture, to understand that the violence against them didn’t mean what they thought it had.

‘It’s got to come out’

It takes a while for psychoactive drugs to work their way through the FDA approval process. MAPS has been testing MDMA-assisted therapy for PTSD for more than a decade. Many of the early participants experienced lasting improvement.

Rachel Hope, who experienced a cascade of abusive events as a child that left her with severe PTSD, “did 20 years of psychotherapy” prior to participating in an MDMA-assisted therapy session. “When I got into the outer limits of the really hardcore stuff, I’d start to destabilize and get sicker … I’d start vomiting or have to leave the room. I knew that I had to tell it — the story has a soul of its own. It’s got to be seen, got to be known. It’s got to come out. But I couldn’t get it out,” she says.

Hope had had good therapists and managed to run a real estate development company, but eventually the PTSD got so bad she couldn’t leave the house. Finally her personal assistant threatened to quit if she didn’t go back into therapy. And that’s how she came to participate in an MDMA-assisted psychotherapy trial in 2005. It was a revelation.

“The MDMA was a terrific antianxiety medicine,” she says; it didn’t make her fuzzy-headed like most antianxiety meds had. “It amplified access to memories and, really, I had access to everything, and I wasn’t terrified. I could actually tell someone, for the first time in my life, what had happened to me. I had so much access to my own mind.” She describes it as the perfect tool to help work through the trauma. “I was rebooting my mind under my own directive,” Hope says.

“They would say things like, ‘Wow. Now I understand the trauma didn’t happen to me because I’m a bad person — I was just in the wrong place at the wrong time.’ And we’re like, ‘Yes! Yes! They finally get it!’”

Williams agrees that the MDMA seems to help patients rapidly make connections and breakthroughs in a single therapy session. Typically, a patient in psychotherapy might have just one such realization every few months.

The participants in the phase 3 trial at UConn Health will have a total of 20 therapy sessions, three of which will include MDMA. Each session will have two therapists present. The MDMA-assisted sessions will be six to eight hours long, after which the participant will stay overnight in the hospital to rest, supervised by a night attendant. And as part of the effort to involve participants from communities of color, all but one of the therapists at UConn Health identifies as an ethnic, racial, and/or sexual minority.

“In Singapore, I was part of the majority, but I was curious how it felt to be Malay, Indian, or one of the other minorities,” says Terence Ching, a clinical psychology doctoral student involved in the study. Ching has also lived in Australia, New Zealand, and Kentucky, where he was not part of the majority ethnic group. “That led me to critically introspect my place in society as someone with many different identities. Having that multifaceted perspective allows me to experience a lot of empathy for people from marginalized groups in the U.S.,” Ching says.

To get a better understanding of what the MDMA-assisted psychotherapy would be like for study participants, Ching participated in a session himself as part of his training.

“It felt like a lot of insights happening constantly,” Ching says. “It’s been a year since the session, and every now and then I have a moment where I remember an insight from it, and/or have another one. It’s a wonderful thing.” Ching hopes that the participants benefit from their MDMA-assisted psychotherapy in the same way he did.

“For someone who has experienced trauma, MDMA-assisted psychotherapy might help them be able to make meaning of it. I really believe in this work,” Ching says.

New Neuroscience Chair Establishes UConn’s First Alzheimer’s Lab

a digital rendering of orange amyloid plaque on blue healthy neurons.

In this rendering, healthy neurons afflicted with amyloid plaques are colored orange. Studies suggest this plaque leads to cognitive decline in patients with Alzheimer’s.


Internationally recognized neurodegenerative disease researcher Riqiang Yan, Ph.D., joined the UConn School of Medicine this spring as chair of the Department of Neuroscience. He has established the medical school’s first research laboratory dedicated to studying and discovering new treatments for Alzheimer’s disease and other neurodegenerative diseases.

Prior to his appointment, Yan served as the Cleveland Clinic’s Morris R. and Ruth V. Graham Endowed Chair Professor and Vice Chair of Neurosciences and professor of molecular medicine at Case Western Reserve University. His five studies that focus on identifying the biological culprits behind Alzheimer’s disease are funded by the National Institutes of Health (NIH).

Yan’s studies build upon his co-discovery of the BACE-1 protein, the critical molecule that he revealed fuels the production of β-amyloid peptides, or plaque buildup, in the brains of Alzheimer’s disease patients. Studies suggest that these peptides are toxic and lead to cognitive decline in patients with Alzheimer’s.

Yan and his team are currently testing in mouse models the power and safety of several promising molecules to target BACE-1 and inhibit its biological function in order to prevent or stop further β-amyloid growth. Just before he arrived at UConn Health, Yan’s team published significant findings in the Journal of Experimental Medicine that showed that removing the BACE-1 enzyme in adult mice with Alzheimer’s reverses the plaque formation that inhibits cognitive function. The study was widely covered by national media.

In addition, Yan and his team are gaining greater insight into the important role reticulon 3 protein (RTN3) plays in the formation of dystrophic neurites in the brain, which can lead to memory loss, dementia, and Alzheimer’s disease in the elderly. The Yan lab is also exploring treatment that aims to enhance neurogenesis to replenish the loss of brain cells in patients with Alzheimer’s and other neurodegenerative diseases.

“We welcome Dr. Yan to UConn School of Medicine and Connecticut, as he and his research programs are very highly respected by leaders and other scientists in the field,” says Dr. Bruce T. Liang, dean of UConn School of Medicine.

Yan’s recruitment brings with it a host of research collaboration opportunities across the School of Medicine and its departments of Neurology, Neurosurgery, and Psychiatry; with the UConn Center on Aging; with neurobiology and brain investigators at the University; as well as with the Jackson Laboratory for Genomic Medicine on UConn Health’s campus.

“I look forward to working with my colleagues at UConn to expand creative research in neurosciences,” says Yan, who earned his Ph.D. from the University of Kentucky and completed a postdoctoral fellowship at The Rockefeller University. “It is my passion and desire to mentor our talented UConn neuroscientists and staff and watch their lists of research, discoveries, and accomplishments grow even greater, along with more national recognition of their efforts.”

He adds: “We all have a hope that in 5 to 10 years, with academia collaborating with pharmaceutical companies, we will indeed have an effective drug to finally treat Alzheimer’s disease.”

There has not been an FDA-approved drug to try to treat the disease since 2002, Yan says. “It’s our big hope, and we will continue to try hard at UConn to discover and test a new, effective drug therapy to make this hope a reality to help those struggling with Alzheimer’s and ease the burden of future patients and their families.”

Class of 2009 Med Students Return to Practice at UConn Health

Class of 2009 reunite. From left: Dr. Sara Tabtabai, Dr. Ben Ristau, Dr. Todd Falcone, and Dr. Marilyn Katz

From left: Dr. Sara Tabtabai, Dr. Ben Ristau, Dr. Todd Falcone, and Dr. Marilyn Katz


TThe UConn School of Medicine graduating class of 2009 is experiencing a mini-reunion at UConn Health, with five doctors from the class now practicing here.

Dr. Todd Falcone (ear, nose, and throat), Dr. Marilyn Katz (internal medicine), Dr. Ben Ristau (urologic oncology), Dr. Sara Tabtabai (cardiology), and Dr. Rafael Pacheco (radiology) came back with fond memories of their time as UConn medical students.

Katz says she knew the UConn School of Medicine was a match right away. “I loved everyone I met on my interview day — students, faculty, and staff — and canceled all my other interviews once I received my acceptance.”

Falcone joined UConn Health in 2014. “I had an excellent time here, and I credit the School of Medicine for preparing me to match into a competitive residency program and become a competent and caring physician and educator. I do not believe I could have received a better medical school education anywhere else.”

The five physicians say their medical school connections help them deliver better patient care today. “Rafael Pacheco and I were medical interns together as he was doing his prelim year prior to radiology,” Katz shares. “It was great to discuss similar patient cases with him then, and knowing I can call him now to discuss testing is a huge benefit as a primary care physician.”