Newsletter, December 2019

�� State Researchers Find a Way to Potentially Conquer Cancer Drug Resistance

Free stock image of a Breast Cancer Awareness walk

An article published by �� researchers in a high-impact journal may help to develop more effective drug treatments for one type of invasive breast cancer.

Breast cancer affects nearly 250,000 Americans every year, killing more than 41,000, according to the United States Centers for Disease Control and Prevention. Some cancer cells are more aggressive and prone to metastasize. A type of cancer called HER2-positive breast cancer is one of them.

HER2-positive breast cancer represents approximately 20 percent of cases. For this type of breast cancer, the gold standard treatment is an anti-HER2 therapy, which includes the use of a drug such as Lapatinib (Tykerb) and Trastuzumab (Herceptin). While anti-HER2 therapy remains popular, one of the biggest concerns is development of drug resistance. Indeed, many of the patients eventually develop resistance to anti-HER2 therapy.

Dr. Manabu Kurokawa, Assistant Professor of Biological Sciences in �� State’s College of Arts and Sciences, and his research team recently published a paper in Cell Reports, "," which shows how cancer cells develop this resistance and how researchers and oncologists might combat it.

“We found that when breast cancer cells acquire resistance to HER2 inhibitors, they switch their lipid metabolism and prefer eating fat (lipids) rather than making it,” he said. Compared to normal healthy cells, cancer cells need an excessive amount of lipids, presumably to support fast proliferation, Kurokawa says. It is known that, in general, cancer cells like to produce lipids internally for their own use. “There is a channel called CD36 whereby cells can acquire external fat, and during anti-HER2 treatment, breast cancer cells start expressing a lot of CD36, which allows cells to take up more external fat. Interestingly, if you break that mechanism, then they die.”

While studying how breast cancer cells develop that resistance, Kurokawa’s team discovered the cells’ increased appetite for external fat. By exposing naïve drug-sensitive breast cancer cells to low, but steadily increasing, doses of Lapatinib, the team showed they built a resistance. “This method mimics clinical setting where patients take lapatinib daily and develop resistance,” Kurokawa explained.

“Then when we analyzed any difference in gene expression patterns between drug-sensitive and resistant cells, we saw the genes that regulate lipid metabolism were highly upregulated in the resistant cells,” he said. Up-regulation of CD36 was further validated in breast cancer patients’ cohorts as well as in mouse studies.

“The next question is where does the fat go? In other words, why do cancer cells need exogenous lipids to overcome anti-HER2 therapy? We don’t know,” he said. “Resistant cells may be using the fat as an energy source, for example. If that is the case, the next question would be: can we come up with a diet-based strategy to prevent drug resistance?”

Media Contact
Dan Pompili: 330-672-0731, dpompili@kent.edu

�� State Education Researchers Receive Million-Dollar Grant for Cross-disciplinary Training in Early Childhood Professions

Preschool children learning sign language (free stock photo)

Ohio, like many states, suffers from a teacher shortage, especially in early childhood education and special education. The Buckeye State also is in need of more school psychologists, analysts say.

It’s fortunate, then, that the Office of Special Education Programs just awarded a million-dollar grant to two �� researchers to train teachers and school psychologists in those fields.

Dr. Ching-I Chen and Dr. Kizzy Albritton, assistant professors in the School of Lifespan Development and Educational Sciences in �� State’s College of Education, Health and Human Services, received a five-year, $1.13 million grant for their project, “Interdisciplinary Preparation in Early Education Professions (Project INPREP), to train education professionals who can not only fill those gaps, but also collaborate in a way that bridges the gaps between those fields in the schools.
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“This personnel preparation grant is for the Special Education and School Psychology programs to collaborate with each other so we can train our master’s level students together,” Chen said. “The project scholars enrolled under the Special Education program will be individuals who have an existing teaching license in early childhood education or in K-12 special education, and they’re interested in working in preschool inclusive settings.”

After two years, Chen’s students will receive a master’s degree in special education as well as an endorsement in preschool special education.

“For the School Psychology program, we have a three-year master’s/specialist-level program,” Albritton said. “For the ensuing years, they’ll be part of the training grant, and in the third year, students in our program go to a full-year paid internship.” That internship is funded through the State of Ohio Department of Education.

Chen and Albritton said many preschool special education teachers often only have a general understanding of school psychologists’ roles.

Many preschool special education teachers only know you can use the school psychologist when conducting assessments, and when evaluating whether children are eligible for preschool special education services,” Chen said. “They don’t know school psychologists are also great resources for providing developmental, academic, and social emotional supports as well. So, when they are in their training period, why not teach them how to work with school psychologists, then when they’re in the field they’ve had the experience of teaming up, and it’ll be easier transitioning to the real world.

 Albritton said both of them have been waiting on an opportunity like this one.

“A lot of our coursework in the field of school psychology focuses on K-12 populations,” she said. “So, as a faculty member and researcher, my goal has been to move the field to focus more on early childhood, because if we’re going to do early intervention, it doesn’t get much earlier than preschool.

Chen said the project scholars will work in the classroom at least one day each week with general educators in early childhood education, learning to support all children while also providing individual support for children who need it. They will also work closely with a school psychologist at the preschool level.

Project scholars will take shared courses in consultation models and theories, typical and atypical childhood development, and also interventions for culturally diverse students. They will also complete action research projects with a collaborating field professional and a focus child, which will enhance their practicum experiences.

�� state will work with the on the project.

“They’ve been great partners,” Albritton said. “Our students have completed internships and practicum with them before. We chose them for that reason, and because they also provide preschool services for about 10 school districts. So, with that, hopefully the project scholars will be able to see a wide range of different settings.”

Media Contact
Dan Pompili: 330-672-0731, dpompili@kent.edu

�� State Healthcare Design Researcher Receives $2.47 Million to Design Safer and More Efficient Level I Trauma Rooms

Sara Bayramzadeh, Ph.D., serves as coordinator and Elliot Professor in the Healthcare Design Program in ��'s College of Architecture and Environmental Design.

Traumatic injuries are the third leading cause of death nationally and the first in Americans age 44 and younger, according to the U.S. Centers for Disease Control and Prevention. Level I trauma rooms are intended to stabilize and save the lives of patients with the most severe traumatic injuries. The Agency for Healthcare Research and Quality has awarded a $2.47 million grant to Sara Bayramzadeh, a �� researcher, to help create trauma rooms that support staff in saving patients’ lives.

NSF Award Helps �� State Anthropologists Expand International Partnership

A bonobo stares back at the camera while another walks away

A new federal grant will help �� expand an international relationship and provide invaluable opportunities for some graduate students.

The (NSF) recently awarded �� State a three-year $298,000 International Research Experience for Students (IRES) grant that will allow graduate students to travel to in Japan to study primates and human evolution at the world-renowned .

The IRES grant is under the direction of Dr. Anthony Tosi, associate professor of anthropology in the College of Arts and Sciences, along with his colleagues in the department, Dr. Richard Meindl, professor and graduate coordinator; Dr. Owen Lovejoy, distinguished professor; and Dr. Mary Ann Raghanti, professor and chair.

“The theme here is that we’re using non-human primates as models for human evolutionary history,” Tosi said. “Under this umbrella, we’ve allowed for several smaller projects, yet to be created, to be done by 18 graduate students — six students each summer for the next three years.”�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ

Tosi said the students will come from anthropology and biological sciences, and they will conduct studies focused on morphology, genetics, neuroscience, and primate behavior.

“Ideally, these might be master's and doctoral students, who would plug this in as a chapter in their final project, as one component that will somehow dovetail with what they already do,” Raghanti said.

�� State Biologist Lands NIH Grant to Research Cannabinoids’ Effect on Sleep Cycles

Stock photo of a blonde woman in red pajamas sleeping

There are two cycles most people can’t avoid — sleep and the news. And If you’re awake, you can’t help hearing the news reporting about cannabinoids. A �� State researcher may soon have news about how these substances affect our body’s natural clock.

Dr. Eric Mintz, Professor of Biological Sciences and Associate Dean in the College of Arts and Sciences, studies the human body’s circadian rhythms, which affect the sleeping-waking cycle.
Not as well-known is how the brain’s other systems work in concert with that clock or what happens to it when we interfere with them.

The at the U.S. recently awarded Mintz a three-year, $446,000 grant to study the effect of the cannabinoid system on circadian rhythms.
People mostly acquire cannabinoids externally either from THC (tetrahydrocannabinol) in marijuana, or cannabidiol (CBD) oil manufactured from hemp.

“Inside our brains, we make our own cannabinoids” Mintz said. “They’re something else, and part of the normal function of the brain’s systems.”

The cannabinoid system works in tandem with many others, like the nervous system (sensation, pain) and the limbic system (emotions, learning, memory), and the hypothalamus (metabolism and body temperature) and cannabinoids are known to stimulate these, often bringing relief from pain or anxiety, and stimulating the appetite. The cannabinoid system also affects our circadian rhythms, but we’re uncertain how.

“So the first part of this question is: If we stop the system from working, if we block it in some way, does that alter how the clock works?” he said. “The primary the focus of the grant is to look at the system’s normal function so we can ultimately understand, if we mess with it, what are we messing with.”

After that, Mintz said, the study will analyze how introducing external cannabinoids like THC or CBD may affect circadian rhythms. Mintz said literature on cannabinoids is limited because they don’t affect study subjects the same as other drugs do, which makes the research more complicated to carry out and more difficult to analyze.

“Most research on drugs, and how they affect the brain, is done on drugs where the major issue is addiction, and the drugs may have all kinds of physiological effects,” he said. “The focus here isn’t on addiction and withdrawal, the focus here is on what does it actually do. Are there consequences? There could be positive consequences too, we just don’t really know.”

Mintz said that despite starting from a small base of knowledge, he’s hopeful the project will yield a better understanding about the relationship, and even provide a foundation for cannabinoid dosing studies.

“If you live in Colorado, and you’ve gotten into the habit of having a hard day of work, coming home and taking some THC, and you do so the same time every day, how does that affect your sleep?” he said. “Do you get better sleep, more sleep, less? We have no idea. All we have is people’s anecdotes, but those are notoriously unreliable, because people may like how the drug makes them feel, and report that they’re sleeping better when maybe they’re not.”

MEDIA CONTACT
Dan Pompili: 330-672-0731, dpompili@kent.edu

Manabu Kurokawa, Ph.D., Assistant Professor of Biological Sciences at �� State

HER2-positive breast cancer represents approximately 20 percent of cases. For this type of breast cancer, the gold standard treatment is an anti-HER2 therapy, which includes the use of a drug such as Lapatinib (Tykerb) and Trastuzumab (Herceptin). While anti-HER2 therapy remains popular, one of the biggest concerns is development of drug resistance. Indeed, many of the patients eventually develop resistance to anti-HER2 therapy.

Dr. Manabu Kurokawa, Assistant Professor of Biological Sciences in �� State’s College of Arts and Sciences, and his research team recently published a paper in Cell Reports, "," which shows how cancer cells develop this resistance and how researchers and oncologists might combat it.

“We found that when breast cancer cells acquire resistance to HER2 inhibitors, they switch their lipid metabolism and prefer eating fat (lipids) rather than making it,” he said. Compared to normal healthy cells, cancer cells need an excessive amount of lipids, presumably to support fast proliferation, Kurokawa says. It is known that, in general, cancer cells like to produce lipids internally for their own use. “There is a channel called CD36 whereby cells can acquire external fat, and during anti-HER2 treatment, breast cancer cells start expressing a lot of CD36, which allows cells to take up more external fat. Interestingly, if you break that mechanism, then they die.”

While studying how breast cancer cells develop that resistance, Kurokawa’s team discovered the cells’ increased appetite for external fat. By exposing naïve drug-sensitive breast cancer cells to low, but steadily increasing, doses of Lapatinib, the team showed they built a resistance. “This method mimics clinical setting where patients take lapatinib daily and develop resistance,” Kurokawa explained.

“Then when we analyzed any difference in gene expression patterns between drug-sensitive and resistant cells, we saw the genes that regulate lipid metabolism were highly upregulated in the resistant cells,” he said. Up-regulation of CD36 was further validated in breast cancer patients’ cohorts as well as in mouse studies.

“The next question is where does the fat go? In other words, why do cancer cells need exogenous lipids to overcome anti-HER2 therapy? We don’t know,” he said. “Resistant cells may be using the fat as an energy source, for example. If that is the case, the next question would be: can we come up with a diet-based strategy to prevent drug resistance?”

Media Contact
Dan Pompili: 330-672-0731, dpompili@kent.edu

Return to December 2019 Newsletter

�� State Education Researchers Receive Million Grant for Cross-disciplinary Training in Early Childhood Professions

�� State Healthcare Design Researcher Receives $2.47 Million to Design Safer and More Efficient Level I Trauma Rooms

NSF Award Helps �� State Anthropologists Expand International Partnership

�� State Biologist Lands NIH Grant to Research Cannabinoids’ Effect on Sleep Cycles

Kizzy Albritton, Ph.D., assistant professor in the School of Lifespan Development and Educational Sciences at �� State

Ching-I Chen, Ph.D., assistant professors in the School of Lifespan Development and Educational Sciences at �� State

Dr. Ching-I Chen and Dr. Kizzy Albritton, assistant professors in the School of Lifespan Development and Educational Sciences in �� State’s College of Education, Health and Human Services, received a five-year, $1.13 million grant for their project, “Interdisciplinary Preparation in Early Education Professions (Project INPREP), to train education professionals who can not only fill those gaps, but also collaborate in a way that bridges the gaps between those fields in the schools.
�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ�ċ
“This personnel preparation grant is for the Special Education and School Psychology programs to collaborate with each other so we can train our master’s level students together,” Chen said. “The project scholars enrolled under the Special Education program will be individuals who have an existing teaching license in early childhood education or in K-12 special education, and they’re interested in working in preschool inclusive settings.”

After two years, Chen’s students will receive a master’s degree in special education as well as an endorsement in preschool special education.

“For the School Psychology program, we have a three-year master’s/specialist-level program,” Albritton said. “For the ensuing years, they’ll be part of the training grant, and in the third year, students in our program go to a full-year paid internship.” That internship is funded through the State of Ohio Department of Education.

Chen and Albritton said many preschool special education teachers often only have a general understanding of school psychologists’ roles.

Many preschool special education teachers only know you can use the school psychologist when conducting assessments, and when evaluating whether children are eligible for preschool special education services,” Chen said. “They don’t know school psychologists are also great resources for providing developmental, academic, and social emotional supports as well. So, when they are in their training period, why not teach them how to work with school psychologists, then when they’re in the field they’ve had the experience of teaming up, and it’ll be easier transitioning to the real world.

 Albritton said both of them have been waiting on an opportunity like this one.

“A lot of our coursework in the field of school psychology focuses on K-12 populations,” she said. “So, as a faculty member and researcher, my goal has been to move the field to focus more on early childhood, because if we’re going to do early intervention, it doesn’t get much earlier than preschool.

Chen said the project scholars will work in the classroom at least one day each week with general educators in early childhood education, learning to support all children while also providing individual support for children who need it. They will also work closely with a school psychologist at the preschool level.

Project scholars will take shared courses in consultation models and theories, typical and atypical childhood development, and also interventions for culturally diverse students. They will also complete action research projects with a collaborating field professional and a focus child, which will enhance their practicum experiences.

�� state will work with the on the project.

“They’ve been great partners,” Albritton said. “Our students have completed internships and practicum with them before. We chose them for that reason, and because they also pr

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