College of Graduate Studies

Researchers study link between lung cancer, thrombosis

PUBLISHED ON Nov. 6, 2017

Cancer is the second leading cause of death in the United States, but did you know that many of these deaths are because of blood clotting?

Clots form when specialized blood cells called platelets detect a tissue injury or receive a clotting signal from another cell. Platelets then become activated, releasing proteins into the blood and onto their own surface. These surface proteins act like glue, causing platelets to stick to each other and to blood vessel walls. The platelets form a plug to patch the torn blood vessel. The platelet proteins released into the blood will attract more platelets and immune cells to the injured site and help the wound to heal.

Dr. Claire Meikle is researching how platelets contribute to thrombosis in cancer patients.

Blood clotting is important to stop bleeding and heal injuries like cuts and scrapes, but sometimes clots form inside the blood vessel, blocking blood flow. When a clot forms inside a blood vessel, it prevents delivery of oxygen and nutrients to organs like the heart or brain. This kind of clot, called thrombosis, can lead to serious problems, including heart attacks and strokes.

Have you ever been warned about blood clots when you take a long airplane or car ride? Sitting still for an extended period of time allows blood to pool in your legs and reduces blood flow throughout the body. Because the blood isn’t moving, it increases risk of clots forming in the leg veins, a condition called deep vein thrombosis.

These clots are especially dangerous because they can grow to be very large and, if dislodged from the leg, they can travel through the bloodstream and get stuck in the smaller blood vessels in the lungs. This means that the blood will not be able to take fresh oxygen from the lungs to other organs and tissues in the body.

In healthy, active people risk of deep vein thrombosis is very low, and standing and walking around can be enough to prevent leg clots from forming. However, certain diseases can also make deep vein thrombosis more likely. Cancer patients are at especially high risk of thrombosis. We don’t know exactly why this is, but researchers are studying how cancer cells can make platelets more likely to form a clot. It is thought that cancer cells send pro-clotting signals to platelets, leading to a phenomenon called cancer-associated thrombosis.

Cancer patients are about five times more likely to experience thrombosis than healthy people. In fact, thrombosis occurs in as many as 20 percent of cancer patients, causing thousands of deaths each year. Chemotherapy used to treat cancer further increases the risk of thrombosis.

What can doctors do to help prevent cancer-associated thrombosis? First, clinical lab tests are used to measure a patient’s risk for clotting. In high-risk patients, drugs such as heparin can help to reduce clot formation. However, cancer patients taking these drugs are still at higher risk for clotting than people who don’t have cancer. Other health risks, including increased bleeding, are associated with taking heparin for an extended time. A better understanding of what causes clotting in cancer patients could help us develop a safer and more effective way to prevent these clots from occurring.

Platelets also help cancer cells spread to new sites in the body, a process called metastasis. Platelets do this by physically protecting cancer cells from being detected and then killed by other immune cells. Activated platelets can also release proteins that help neighboring blood vessels grow and help cancer cells survive as the cancer spreads. On top of all of this, cancer cells can trigger platelets to activate even more, increasing the risk of cancer spread and more blood clotting. This creates a vicious cycle of platelet activation and cancer spread. We don’t yet know how this cycle starts, or how to prevent it.

My research with Randall Worth at the University of Toledo College of Medicine, formerly the Medical College of Ohio, focuses on how platelets contribute to thrombosis in cancer patients, and how platelets in cancer patients differ from platelets in healthy people.

Lung cancer is the No. 1 cancer killer in the United States, and lung cancer patients are among those with the highest risk of clotting, so I am focusing on this high-risk population for my research.

I obtain blood samples from patients who have lung cancer and from healthy volunteers. I then analyze the platelets by labeling different kinds of cells with different colors, which can then be detected by a laser in a special machine. The machine will count the cells of each color. I can then compare the data across patients to look for differences.

I have found that platelets alone are not more likely to form clots in cancer patients, but they are more likely to interact with other immune cells. My next step will be to determine the mechanism of how platelets attach to immune cells. I will also explore how this attachment might affect platelet activity and the risk of thrombosis.

Further research will help us understand why lung cancer patients are more likely to develop a clot, and what we can do to prevent clots from forming. Our goal is to identify specific proteins that are involved in these cancer-specific interactions. This would allow us to develop a drug to stop only the interactions that lead to thrombosis while allowing platelets to continue doing their usual job of healing cuts and scrapes.

Additionally, this research could help doctors understand when it could be helpful to prescribe a drug that inhibits platelet activation. We anticipate that our work will help prevent clotting in high-risk patients and, ultimately, save lives.

Claire Meikle is an M.D./PhD student in the department of medical microbiology and immunology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Ms. Meikle is doing her research in the laboratory of Randall Worth. For more information, contact or go to

Brandon Tucker, a member of our Michigan Community College Leadership Doctoral Cohort, Crain’s forty under 40 for the class of 2017


Brandon Tucker has always had a passion to help others succeed. So when Washtenaw Community College received a $4.4 million Community College Skilled Trades Equipment Program (STEP) grant from the State of Michigan — matched by their board with $3.6 million — Tucker wanted it to mean more than building renovations and equipment.

Through Tucker’s leadership, the college retooled its curriculum to align with the new technology the grant brought in, focusing on autonomous and connected vehicles.

“Our goal at WCC is to help prepare the workforce for what is not coming, but is already here.” — Brandon Tucker

“We saw the need and where the industry was going, like the need to train the technicians that support the engineers,” Tucker said, also crediting WCC president Dr. Rose B. Bellanca for her vision. “Our goal at WCC is to help prepare the workforce for what is not coming, but is already here.”

The new direction also allows WCC to partner with organizations like University of Michigan’s MCity, the world’s first controlled environment designed to test connected and autonomous vehicle technologies, and the Square One Education Network, which provides grants to educators developing tomorrow’s workforce. These partnerships allow students to graduate from the program more well-rounded and with hands-on experience.

Tucker said the new program has received nothing but great reviews from both students and the industry since its 2016 launch.

“Everyone needs education, inspiration, and empowerment,” said Tucker, who is also an assistant preacher with a mission to serve. “Nothing excites me more than when a person achieves even greater success than they thought possible.”


Mengjie Wang, Ph.D. Student – Special to The Blade | Early puberty can lead to health problems later in life

PUBLISHED ON Nov. 6, 2017

We all go through puberty, the period of time when children physically and emotionally develop into young adults. Puberty happens when a part of the brain called the hypothalamus tells the body to release male or female hormones. In response, height and weight increase, and male or female characteristics begin to develop.

Puberty is considered early if it occurs before a girl is 8 years old or a boy is 9 years old. Around the world, puberty is starting earlier than it once did. Today, about one in 5,000 children goes through early puberty. The known risks for these children can include childhood bullying for body changes, short adult height, and an increased risk of breast cancer.

A clearer understanding of all risks of early puberty is important to patients and physicians.

Mengjie Wang is a PhD graduate student at the University of Toledo College of Medicine and Life Sciences biomedical science program.

Central precocious puberty is a common type of early puberty that involves your hypothalamus. In most cases, we don’t yet know what causes this, but brain tumors, injury, or inflammation are some of the causes.

A child going through puberty needs enough energy to have normal development. An obese child actually provides more energy than the child needs for normal development. This extra energy sends incorrect signals to the hypothalamus for puberty to start. Obesity and early puberty are serious health issues in the United States.

I study how the hypothalamus part of your brain controls obesity, puberty, and reproduction in our lab at the University of Toledo College of Medicine and Life Sciences, formerly the Medical College of Ohio.

We overfed female mouse models by giving them high-fat- diets from the day they deliver their pups until weaning (21 days) to investigate the potential effects of obesity and overfeeding in breastfeeding mothers. Surprisingly, we found that overfeeding the mothers during breastfeeding can cause obesity in the pups and significantly advance the start of their puberty.

This is the first evidence showing that overfeeding during breastfeeding influences obesity and puberty in the offspring.

Does early puberty, caused by overfeeding, also cause other health problems? We did glucose (sugar) tolerance tests and insulin tolerance tests to determine if these pups would develop diabetes when they became adults at 3 months old. We measured blood glucose levels every 15 minutes after giving them a large dose of sugar. Surprisingly, we found that these overfed mice could not keep their glucose levels within normal range. After we gave them insulin, which usually lowers blood glucose, their blood glucose measure did not fall.

These results show that overfed mice from overfed mothers are glucose intolerant and insulin insensitive. This means that obese mice with early puberty also have increased risk of developing diabetes during adulthood.

We then performed a fertility test on the obese mice when they were 4 months old. This tests the adults’ ability to reproduce. Notably, these experiments showed that female mice have trouble getting pregnant and have fewer pups than normal. Therefore, our studies also show evidence that obesity-induced early puberty can also contribute to reproductive problems during adulthood.

Another important player in the effects of childhood obesity is something called Insulin-like growth factor-1 (IGF-1). This is a protein secreted from the liver that regulates body growth and puberty. The hypothalamus in your brain can sense changes in IGF-1 levels and provides feedback signals to regulate IGF-1. We know that there are specific cells in the hypothalamus, called leptin-responsive cells that have IGF-1 receptors. This means that these specific cells can receive signals from IGF-1.

We used research methods to delete the IGF- 1 receptors in those leptin-responsive cells in the hypothalamus and then we tested these mice. We discovered that loss of IGF-1 receptors in otherwise normal mice will cause decreased body weight, along with delayed puberty and reproductive problems. This is the first evidence that IGF-1 receptors in leptin-responsive cells in the brain is important to normal body weight, puberty, and reproduction.

Doctors don’t always follow the same patients from puberty to adult life. Therefore our findings can alert doctors and patients with early puberty that other health problems may arise after they become adults. Correct treatment and follow-up are both important for patients with early puberty.

Mengjie Wang is a PhD graduate student at the University of Toledo College of Medicine and Life Sciences biomedical science program. She is completing her doctoral studies in the Molecular Medicine track in the lab of Jennifer Hill. For details, email or go to​med/​grad/​biomedical.

Medical advances to seek blood test for determining cancer risk

PUBLISHED ON Oct. 1, 2017

Cancer is one of the deadliest human diseases and will affect almost 40 percent of men and women at some point in their lives. While each type of cancer is different, they all share one common theme: They start from a single cell and develop the ability to divide uncontrollably. Determining our risk for getting cancer is complicated because there are many factors, both inherited and environmental, that play a role.

By understanding our own genetics, it may be possible to identify people at greatest risk, allowing us to prevent or diagnose cancer early. As the rate of cancer rises around the world, wouldn’t it be useful to know if you were at greater risk based on your own genetic profile?

The human genome serves as your genetic playbook and contains about 20,000 genes composed of DNA building blocks strung together just like letters to form words. Each cell in your body activates different genes in this playbook to carry out specific functions. Throughout life, your cells are exposed to things that can cause damage to these genes, such as ultraviolet rays from the sun, environmental and household chemicals, and even natural processes associated with aging. Left uncorrected, this damage can lead to permanent changes in these genes called mutations.

Luckily, we have a variety of DNA repair and tumor prevention genes that work together to monitor the genome for damage and stop uncontrolled cell growth. Proteins produced by these genes serve as safeguards to ensure that cells with damaged DNA do not divide. Despite these protective safeguards, some DNA damage is left uncorrected, leading to mutations. While most mutations are harmless or cause a cell to die, some may occur in genes that control cell division. If a cell collects enough mutations in these critical genes, that cell may begin to divide more than normal, resulting in cancer.

Our cells may gain mutations either by inheriting them from our parents, or by collecting them throughout life.

Daniel J. Craig

The inherited mutations are present in every cell and only a few may affect risk for cancer. The mutations that we collect over time occur only in certain cells because of unrepaired DNA damage. The vast majority of human cancers are caused by a lifetime of collected mutations, which is why most cancers occur later in life.

While some inherited mutations can contribute to the risk of cancer if present in a cancer-related gene, additional mutations must also occur in a cell to overcome our genetic safeguards.

If a single cell collects multiple mutations that destroy these safeguards, that cell will divide more than it should. We recognize it as a cancer when it produces so many offspring that it interferes with the function of other cells and distorts the tissue around it.

Lung cancer is the deadliest type of cancer in the United States, killing almost 160,000 people each year — more than the next three deadliest cancers combined (breast, colon, and prostate), and about 20 percent of lung cancer cases occur in non-smokers. Early diagnosis is important because it gives doctors the chance to treat the disease when it is curable. For example, among lung cancers that are diagnosed through screening, 85 percent are in an early stage and can be cured with surgery. Without screening, the majority are in late stage and cannot be cured.

The research in our lab is focused on developing tests to diagnose cancer as early as possible and to identify people who may be at increased risk later in life because of a combination of factors.

My research focuses on developing a blood test that allows us to identify both the mutations that we inherit and those that we collect over our lifetime. Our idea is simple: If a person collects mutations at an unusually rapid rate, he or she likely does not repair DNA very well, and there is a higher likelihood of mutations in critical safeguard genes. This leads to an elevated risk for developing cancer.

This information is important because it allows us to look at inherited and environmental factors that contribute to cancer at the same time in a simple blood test. Identifying at-risk individuals before they develop cancer would allow doctors to create, and insurance companies to justify, a personalized screening plan to catch a potential cancer in its earliest stage when it is most treatable. This would not only save lives, but also save tremendously in healthcare spending.

Our research team works closely with researchers and pulmonary physicians at the University of Toledo, the Toledo Hospital, the University of Michigan, Vanderbilt University, Cleveland Clinic, the National Cancer Institute, and many other centers of excellence in lung cancer research. We are grateful for the support received from the National Institutes of Health and the George Isaac Cancer Research Fund.

Daniel J. Craig is a student studying for his PhD in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program, formerly the Medical College of Ohio. Mr. Craig is doing his research in the laboratory of Dr. James C. Willey in the department of medicine. For more information, contact or go to med/ grad/ biomedical.


Advances in the Study of Brain’s Link to Metabolic Syndrome


High blood pressure, high blood sugar, and overweight. Do these conditions scare you? Then the term “metabolic syndrome” should be a full-blown nightmare to you, because this is a combination of all these conditions within the same person. Even worse, metabolic syndrome often leads to heart disease, diabetes, and infertility.

In the United States, about 600,000 people die from heart disease every year, 26 million people have diabetes and 8 million people suffer from infertility. According to the American Diabetes Association, more than 200,000 new cases of Type 2 diabetes are diagnosed every year and many of these diabetic patients also have obesity and infertility issues. These combined illnesses have become known as the metabolic syndrome.

Insulin plays a major role in regulating both diabetes and infertility. Insulin is a molecule released by your pancreas into your blood stream when your blood sugar is high, for example, after you eat a big meal. Insulin directs the excess sugar in your blood to organs such as your liver, muscle, and fat cells to provide your body with stored energy.

We now know that more than 25 percent of men with Type 2 diabetes also have problems with infertility. Because of the increasing number of patients being treated for both infertility and diabetes, there is intense interest in developing less expensive, combined therapy for these conditions.

Iyad Manaserh is a PhD student in the department of physiology and pharmacology at the University of Toledo College of Medicine and Life Sciences Biomedical Science Program.

At the University of Toledo College of Medicine, formerly the Medical College of Ohio, our research team is focused on the brain because we believe that it is the master regulator of the metabolic syndromes.

Why the brain? What is the connection between the brain and insulin levels in your blood?

We know that specific areas in your brain control how much you eat and how your body responds to high blood sugar. Therefore, our research team is testing the idea that insulin also acts in the brain to regulate metabolic syndrome and related problems such as infertility.

Your brain has multiple regions that control diabetes, obesity, and infertility. One of these regions in the brain is called the hypothalamus, and is further divided into many important subregions. Your brain also contains two types of cells; neurons to communicate messages across the brain and glial cells, whose function has been a mystery until recently.

My research uses a mouse model to study how insulin actions in the brain affect diabetes and infertility. My first experimental step was to delete insulin receptors from specific brain glial cells called astrocytes, which become activated when insulin binds to their receptors. I wanted to know what would happen when insulin could no longer activate the astrocytes. I discovered that astrocytes without insulin receptors affect fertility, diabetes, and obesity.

My research project is to investigate insulin signaling in the brain and its effect on reproduction (fertility) and metabolism (diabetes). When I studied fertility in this mouse model, I saw a delay in onset of puberty in the sick mouse model without insulin receptors, when compared to control healthy mice. Also, the sick female mice did not have regular menstrual cycles. I also observed a reduction in brain fertility hormone levels as well as ovary and testis hormone levels in the sick mice. I also found that pregnancy rate for the sick female mouse model was reduced dramatically when compared to that of healthy mice. I found similar results of decreased fertility in the sick male mouse model when compared to healthy mice. All of these findings indicate that insulin activity in brain cells affects fertility in important ways.

When I studied diabetes and obesity in this mouse model, as we had suspected, there were profound effects. The sick mouse model showed an increase in body weight from the first month and become outright obese by 6 months of age (equal to a 35-40 year old human).

This was the first hint that the sick mouse model would eventually become diabetic. Indeed, the sick mouse model is also prediabetic at an early age and becomes diabetic by 6 months of age. I also checked overall fat and muscle content in the sick mouse model and, as expected, I measured increased fat and low muscle content, also confirming obesity in the sick mouse model.

These combined findings indicate that insulin in the brain is critical in treating obesity, diabetes, and infertility. We are planning to use these results to help identify new drugs that will target these conditions simultaneously thereby lowering the cost of using of multiple drugs.

Iyad Manaserh is a PhD student in the department of physiology and pharmacology at the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Mr. Iyad is doing his research in the laboratory of Jennifer Hill. For more information, contact

New Teaching Assistant Training – August 24, 2017

Attention new Fall 2017 Teaching Assistants. For detailed agenda, please Click Here.

BIG FISH: Jessica Sherman Collier, grad student, Finalist for National Fellowship Sea Grant [VIDEO]

A University of Toledo graduate student in biology who has been working to restore giant, ancient sturgeon to Lake Erie was recently selected as one of 61 finalists across the country by Sea Grant for the 2018 Knauss Fellowship.

As a finalist, Jessica Sherman Collier, PhD student researcher in UT’s Department of Environmental Sciences, will spend a year working in Washington, D.C., on water resource policy.

“I am very excited and quite honored to be selected for this fellowship,” said Sherman Collier, who was recommended to Sea Grant by her PhD adviser Dr. Jonathan Bossenbroek. “The Knauss Fellowship is an amazing opportunity, and I am so happy to represent The University of Toledo and the Great Lakes region while I am there.”

Sherman Collier will spend a week in November interviewing with up to 20 different federal agency and legislative offices, such as the National Oceanic and Atmospheric Administration, Department of Interior, National Science Foundation, U.S. Navy, and the Senate Committee on Commerce, Science and Transportation. After being matched with her fellowship placement, her work will begin in February.

“This is a great launch to Jessica’s career, and I hope she finds satisfaction doing work as a public servant for the betterment of our environment,” said Dr. Tim Fisher, geology professor, chair of the UT Department of Environmental Sciences, and interim director of the Lake Erie Center.

“We are excited about the talent and perspectives the 2018 Knauss Fellowship finalists will bring to their executive and legislative appointments next year,” Jonathan Pennock, director of the National Sea Grant College Program, said. “The Knauss Fellowship is a special program for Sea Grant, and we are proud of the professional development and opportunities Sea Grant has provided our alumni, the current class and now these finalists.”

Knauss finalists are chosen through a competitive process that includes several rounds of review.

Since 1979, Sea Grant has provided more than 1,200 early-career professionals with firsthand experiences transferring science to policy and management through one-year appointments with federal government offices in Washington, D.C.

Sherman Collier, who also is president of the North American Sturgeon and Paddlefish Society Student Subunit, has been involved in the project to restore lake sturgeon to Lake Erie. Most recently, she helped the Toledo Zoo secure $90,000 in federal grant money to build a sturgeon rearing facility along the Maumee River, which flows into Lake Erie. Sherman Collier assisted the project by verifying that spawning and nursery habitat still ex

ist in the Maumee River to sustain a population of the fish that can live to be 150 years old and grow up to 300 pounds and eight feet long.

“I have enjoyed working with partners at the zoo, as well as state and federal agencies to give these large and ancient fish a chance to thrive in Lake Erie once again,” Sherman Collier said. “This is an instance when scientists and natural resource managers have the opportunity to improve the state of an ecosystem by restoring a species that belongs there and to learn a good lesson about our actions in the past.”

BIG FISH:  Jessica Sherman Collier, grad student Finalist for national fellowship Sea grant

Thomas Lai, graduate student, awarded Spitzer Fellowship in astronomy

“As a teenager, gazing at the stars on the dark canvas of the sky was like entering the most luxurious cinema,” reminisced Thomas Lai, a graduate student studying astronomy. “Soon I picked up the habit of staying in the dark whenever I could, and to recognize as many constellations as possible during my high school years.

“In retrospect, I can see this as a sparkle of the beginning of my interest in the enigmatic cosmos.”

Lai’s passion and hard work were recognized by the Department of Physics and Astronomy: He recently received the Doreen and Lyman Spitzer Graduate Fellowship.
The fellowship is named after Toledo natives. Lyman Spitzer was a world-renowned physicist and astronomer, who was an early proponent of a project that became the Hubble Space Telescope. The Spitzer Space Telescope, launched in 2003, is named after the scientist. Doreen Spitzer was a prominent archaeologist who had an affinity for all things Greek.

Lai, with assistance from Dr. Adolf Witt, Distinguished University Professor Emeritus of Astronomy, and Dr. JD Smith, associate professor of astronomy, was able to publish a study on light emissions from nebulae in the Cassiopeia constellation.

“I was extremely pleased that we were able to offer the Spitzer Fellowship to Thomas. He was clearly qualified; he was eager to start an independent research project during his first year as a graduate student at UT, which the Spitzer Fellowship made possible,” Witt said. “The data for this project had been secured beforehand by my collaborator, Ken Crawford, and myself. This allowed Thomas to enter right at the data calibration, reduction and analysis stage of the project — the phase where scientific results and conclusions are being extracted from a collection of images and numbers.

“I enjoyed working with Thomas. The fact that the project resulted in a peer-reviewed scientific paper in a major journal within about two years speaks for itself.”

“They showed me not only the method in conducting research, but also the right attitude in finding the reasonable answer,” said Lai, regarding the aid he received from Witt and Smith.

On the results of his study, Lai said, “I am particularly interested in extended red emission, because we understood little about the exact emission process and the carrier involved in producing such light, even though it has been studied for more than 40 years. To summarize this study, we attributed the extended red emission to a fluorescent process, namely the recurrent fluorescence, which enables small and fragile particles in interstellar space to dissipate their energy efficiently after being bombarded by high-energy photons originating in an illuminating star. This mechanism prevents particles from getting destroyed in the harsh environment filled with ultraviolet radiation from stars, and it may be a crucial process for increasing the survival rate of small carbonaceous molecules, which might be the building blocks of life.”

Though great progress has been made, Witt pointed out the work of a scientist is never finished: “It is an important part of the research experience that every successfully completed project should lead to new questions, which then demand follow-up studies. This has been the case with our work as well. A new question has emerged from some of our current findings, the solution to which we are pursuing through observations with the 4.3-meter Discovery Channel Telescope in Arizona and the 10-meter Keck II telescope on Mauna Kea, Hawaii. This will most likely be part of Thomas’s PhD thesis.”

Luckily, Lai’s passion for this field will surely lead to many more years of scientific discovery.

“Having this paper published means a lot to my career in astronomy,” Lai said. “It encourages me to find more intriguing phenomena provided by the universe and to reveal those profound facts hidden by wonders of the nature.”

Teaching Assistant (TA) Training Save-The-Date

Attention new Fall 2017 Teaching Assistants – TA training scheduled for Thursday, August 24th, 8:30-noon, Wolfe Hall Room 1201. More details to follow – Click Here.

Congratulations, Dr. Greg Guzman – Vice President of Institutional Advancement at Winebrenner Theological Seminary in Findlay, Ohio.

Congratulations, Dr. Greg Guzman, a recent graduate of our Higher Education Doctoral program, who has accepted a position as the Vice President of Institutional Advancement at Winebrenner Theological Seminary in Findlay, Ohio.

Dr. Greg Guzman

Click Here to view the Press Release