Bright minds, bright futures for young scientists evident at Cancer Research Day
By Mary Hardin
Monday, June 10, 2019
The months of work involved in probing complex scientific issues was evident in the detailed graphics and technical descriptions on the 135 posters on display May 15 at the 2019 IU Simon Cancer Center Cancer Research Day poster session.
Undergraduate, graduate and medical students, along with post-doctoral and medical fellows, research technicians, clinical nurses and faculty are invited to exhibit information on their research performed in labs at the IU Simon Cancer Center and elsewhere across the state. Cash prizes are awarded each year for the best posters in four categories:
- basic science
- population science/epidemiology
- translational/clinical research
Four of the young scientists took time to explain their research before this year’s event ended.
Winning first prize for his poster in translational science was Ashok Narasimhan, Ph.D., who is researching one of the most recognizable symptoms of cancer, the loss of muscle and fat body mass. Known as cachexia, it has a resounding negative effect on patients because it causes weakness, decreases patient tolerance to treatment and effects quality of life. It compromises survival.
Ashok is a post-doctoral candidate in the lab of Teresa Zimmers, Ph.D., associate professor of surgery at IU School of Medicine and a member of the Tumor Microenvironment and Metastasis research program at IU Simon Cancer Center.
“Most studies focus on muscle wasting and there is little understanding of how fat wasting contributes to cachexia,” Ashok said.
Using muscle and fat tissue from pancreatic cancer patients, Ashok and his team identified 4,416 genes involved in adipose (fat) tissue wasting and 883 genes in muscle tissue wasting contributing to cachexia. His findings showed that the same genetic pathways can be activated in muscle and adipose tissue but different genes were involved in the process. That finding is important, Ashok said, because different mechanisms may be involved in the process of muscle wasting and adipose tissue wasting which provides more opportunities for potential therapeutic interventions.
“That’s important because clinical trials have focused only on muscle wasting and not adipose tissue wasting,” he explained. “This is the first research to identify important common genes between animals and humans, suggesting that there is a core set of genes that can be targeted for therapies.”
He will be first author on the paper about this research to be submitted soon for publication in the Journal of Cachexia, Sarcopenia and Muscle. Ashok, who will complete his second year of post-doctoral research in July, has five other published scientific articles and currently has others in the pipeline.
Ashok has a bachelor’s degree in biochemistry and a master’s degree in biomedical genetics from universities in his native India. His doctoral degree in medical sciences is from the University of Alberta, Canada. He wants to remain in academic research with an ultimate goal of developing novel therapeutics for cachexia in all types of cancer.
Ammara Abdullah, Ph.D., is a post-doctoral research associate in the lab of Purdue University Center for Cancer Research member Michael Wendt, Ph.D., an assistant professor with the Purdue College of Pharmacy. The focus of Ammara’s research is breast cancer metastasis and drug resistance.
This is her second post-doctoral position. Following completion of her doctorate at Kingston University in London, Ammara joined the University of South Dakota where she spent two years doing cancer research. She then decided to leave cancer research to investigate another interest: cardiology. After working for two years in a cardiology lab, Ammara returned to cancer research and joined the program at Purdue.
Interestingly, the day of the poster session was the sixth anniversary of the day she immigrated to the United States to continue her education. A native of Pakistan, Ammara completed her bachelor’s and master’s degrees at the University of Karachi before moving to the United Kingdom.
HER2-positive breast cancer represents about 20 percent of all breast cancers, Ammara said. It can be an aggressive form of the disease and it is not uncommon for patients to develop resistance to the drugs treating the cancer. Ammara is investigating underlying mechanisms that are responsible for failure of anti-HER2 therapy.
The protein, HER2, is present in all breast cells and only becomes a problem when it replicates in an uncontrolled manner, eventually leading to breast cancer. For her project, Ammara’s lab first developed several drug resistant models of breast cancer. The therapy-resistant cells were analyzed and two genes, FGFR1 and Nrp1, exhibited some of the most significant changes as a result of acquired drug resistance.
“We wanted to see if the genes FGR1 and Npr1 are responsible for drug resistance and metastasis,” Ammara said. What they found is that when the genes were allowed to act together, the growth of breast cancer cells was significantly enhanced and metastasis to the lung occurred within a brief period. When the Npr1 was deleted from the process, breast cancer metastasis to the lung was substantially decreased.
Ammara is excited about her findings and intends to submit the research for publication.
Ammara hopes to remain in the United States and work at a cancer research institute such as the National Cancer Institute. She and her husband, who is an industrial engineer, have two pre-school age children.
Sharif Rahmy, M.S., is pursuing his doctoral degree in integrated biomedical sciences at the Mike and Josie Harper Cancer Research Institute at the University of Notre Dame. He works in the lab of Xin Lu, Ph.D., in the Department of Biological Sciences.
Sharif, who is from the Netherlands, completed his undergraduate and master’s degrees at the University of Utrecht. In 2013, he studied at Notre Dame for several months and was so impressed he decided to return to the northern Indiana university for his doctorate.
His poster presentation focused on the most common cancer in men: prostate cancer, which initially is very treatable with five-year survival rates at about 95 percent, Sharif said.
“Androgen deprivation therapy for prostate cancer works well – until it doesn’t – and the patient develops castration resistant prostate cancer,” Sharif said. “When that develops, the five-year survival rate dips to 28 percent.”
Immunotherapy, which is revolutionizing the field of cancer therapy for many other types of cancer, produces only about a 10 percent response rate for men with castration resistant prostate cancer or CRPC. Sharif’s research seeks to understand the process that underlies the lack of respond to treatment in CRPC.
In the lab, Sharif focused on immune checkpoint blockade (ICB), which relies on reactivating the immune system to kill tumor cells. By comparing patterns between ICB sensitive and ICB resistant cell lines, he identified several unique patterns associated with ICB resistance. Using Vorinostat, a chemotherapy that can manipulate the process involved in cell replication, Sharif and his team managed to re-sensitize ICB resistant tumors to ICB treatment, resulting in a response rate of 80 percent. He and his team are currently working to understand how Vorinostat affects the microenvironment of the resistant tumor.
“Our goal is to gain an understanding of ICB resistance in CRPC so we can identify potential drug targets for combination treatment,” Sharif said.
Sharif wants to continue his career in academic research, possibly in the United States, after he completes his doctorate in integrated biomedical sciences.
Photography and kickboxing may be her hobbies, but the true love of Justine Levan, Ph.D., is science – in particular researching how a human papillomavirus manipulates the cell it is infecting to help the virus grow and cause cancer.
HPV is responsible for about 5 percent of cancer worldwide, particularly in low-income counties. Worldwide, cervical cancer is the third most common cancer in women with 80 percent of the cases occurring in the developing world. Head and neck cancers, which also can be caused by HPV, are increasing in frequency in the United States.
“Even though there’s a vaccine, it is still important to know how HPV causes cancer,” Justine said. “The greatest risk for developing cancer from HPV is persistent infection from the virus. Most HPV infections are asymptomatic; we don’t fully understand what causes the persistent infection.”
Her Cancer Research Day poster focused on a high-risk HPV, one of the types of HPV that can cause cancer, and its partnership with a host protein, NFX1-123. This protein is present in different amounts in individuals, which may be a factor in why some people develop persistent infection.
Justine’s research has shown that NFX1-123 is key to the replication of the high-risk HPV. “The partnership changes the cell and cell processes and helps the virus grow and complete its life cycle – which can lead to a persistent infection,” she explained.
The next phase of her research will look at that partnership and how it affects other parts of the virus’ life cycle. By identifying that process, Justine’s lab will seek cellular mechanisms involved and try to identify a potential target to interrupt the process.
Justine followed her mentor, Rachel Katzenellenbogen, M.D., to Indianapolis to begin her post-doctoral fellowship in January. Dr. Katzenellenbogen, an associate professor of pediatrics at IU School of Medicine and the Chuck and Tina Pagano Scholar at the IU Simon Cancer Center, was recruited from the University of Washington School of Medicine in Seattle where Justine completed her doctorate in pathobiology – the biology of infectious diseases.
Although snowy Indiana was a change for Justine, who grew up near Los Angeles and was more familiar with Seattle’s rainy skies, she has found enjoyment in her new home. She finds Indianapolis residents extremely friendly and open and is pleased with the number and diversity of the training opportunities offered student researchers at IUPUI and corporations in the city.
Cancer Research Day
Take a look at the list of winning posters from 2019.
IU Simon Cancer Center Cancer Research Day is an annual event that aims to increase understanding and awareness of IU Simon Cancer Center research endeavors and encourage collaboration with other cancer research institutions in Indiana. Students, fellows and faculty conducting cancer research at IUPUI, IU-Bloomington, Purdue University and the Harper Cancer Research Institute, a collaboration between the IU School of Medicine the University of Notre Dame, are invited to present poster abstracts.