Researcher Vinit Shanbhag

Vinit Shanbhag

Stepping into their own

January 15, 2020 By Mariah Cox in Research Tags: Preparing Future Faculty Program

Two Bond Life Sciences Center researchers find their path in teaching and research

Sarah and Vinit — Sarah Unruh and Vinit Shanbhag have both taken paths that have led them toward teaching positions and fellowships.

By Mariah Cox | Bond LSC

As one semester closes and another begins, Sarah Unruh finds herself at the start of a new chapter of her life—this time at the front of the classroom. A newly appointed assistant professor at Illinois College, Unruh only had a handful of weeks to create syllabi, craft lesson plans and pack up her entire life to prepare for the start of classes on Jan. 14.

For Unruh, a recent Ph.D. graduate in biology in the Chris Pires lab, the quick turnaround and placement at Illinois College was somewhat serendipitous in her career timeline. Throughout her doctoral program, Unruh always thought her next step would be a postdoctoral fellowship.

“Toward the end of my Ph.D. I really could have taken a little bit more time, but my collaborator emails me out of the blue with a job that might be interesting if the timing works,” Unruh said. “There was no mention of where it was just a link to the application.”

So, Unruh took the leap and applied for the position this past February. And, get this—it was the only thing she applied for post-graduation.

Although the college was looking to fill a faculty gap for the fall semester, her connection with a colleague allowed time for her to finish her degree and begin the position in the spring. After an arduous application and multi-step interview process, Unruh is pleasantly surprised about the opportunity before her and is looking forward to becoming an established faculty member in her new home.

During her doctoral program, Unruh taught labs through assistantships for a handful of classes including plant systematics, genetics and botany. While many of Mizzou’s classes can often enroll more than 100 students, she fell in love with the small classes that science labs afford.

“When I applied, I really liked the idea of a smaller school and being able to invest in students in a smaller classroom setting,” Unruh said. “When I was a TA, my role was facilitating the lab based on content provided by the professor. However, for plant systematics, I had to come up with the writing-intensive curriculum and that was a really good experience. In addition to working with the students, I was able to critically think about what makes a good assignment and what I wanted them to learn.”

Unruh is not a tenure track faculty yet, but she hopes to covert to tenure track within the next couple of years. In the spring she will teach molecular cell biology and introductory biology, each with a lab. Additionally, she will have her own research lab that will study the interaction between mycorrhizal fungi and endangered orchid species.

Illinois College is an undergraduate institution that heavily encourages students to participate in research opportunities. With her experience mentoring student researchers in the Pires lab, Unruh is especially excited about that aspect of her position.

“The relationships I’ve really forged [here at Mizzou] have been with the students that come to the lab,” Unruh said. “Through my teaching assistantships, I really liked and do still like interacting with the students.”

For Unruh and many other students like her, her discovery of research scientist and professor as a career path is backed by a long list of experiences and steppingstones that directed her path. Unruh knew she wanted to teach the summer after her freshman year of high school when she became a volunteer and then camp counselor at the St. Louis Zoo, a position she stayed at for seven summers.

“That was where I fell in love with education as something I could do, and not only liked it, but realized I wanted to do that and was good at it,” Unruh said. “It was a space where I came into my voice a little bit because I’m definitely an introvert, but there you have to learn how to get kids excited and be really loud and present.”

From there, her research in the Pires lab solidified her desire to become a professor, rather than teach K-12.

Unruh is not alone in pursuing teaching opportunities after earning a Ph.D.

Current Bond LSC researcher Vinit Shanbhag is also on the path to soon step into a research scientist and professor role. In 2018, Shanbhag was selected for the Preparing Future Faculty (PFF) Program, a one-year program that seeks to prepare doctoral students and postdoctoral scholars for future faculty roles and job expectations.

Through the program, Shanbhag was able to be an independent instructor for undergraduate-level biochemistry courses. Other aspects of the program included continuing research in Michael Petris’ lab and engaging in professional development opportunities. This highly competitive fellowship program accepts only four fellows from applicants worldwide.

“After my fellowship, I’m leaning toward an academic rather than an industry position. With tenure track faculty positions, there’s a teaching requirement. The program helped increase my confidence in my teaching skills,” Shanbhag said.

After finishing up his current research project in the Petris lab, Shanbhag is looking forward to applying to an R1 or R2 institution and setting up his own lab with the goal of continuing his research on copper and cancer.

“The fellowship was great. Especially being an international fellow, I wasn’t sure whether my students could understand my English,” Shanbhag sad. “I got good reviews from the students so that allowed me to analyze what I was doing right and what I could improve on.”

From various volunteering, teaching, fellowship or research experiences, the path to becoming a research professor looks different for everyone. But one thing’s for certain—they’re all invested in contributing to science and inspiring the next generation to do so as well.

Stopping transport: How limiting copper can combat cancer

December 30, 2019 By Mariah Cox in Research Tags: Michael Petris, Vinit Shanbhag

Michael Petris and lab — Vinit Shanbhag (left) is pictured with a few of his co-collaborators Nikita Gudekar, Michael Petris (principal investigator), Kimberly Jasmer and Aslam Khan (from left to right). | Photo by Jinghong Chen, Bond LSC

By Mariah Cox | Bond LSC

We find copper in currency, electrical equipment and jewelry, but it also plays an essential role within our bodies. From its use in the production of red blood cells to maintaining healthy bones, blood vessels, nerves and immune function, a tiny level of copper makes us function.

But recent research points to a darker side: its function in cancer. Numerous animal studies have demonstrated that elevated levels of copper are found in tumors suggesting a critical requirement of this nutrient in tumor growth. Subsequent clinical trials have shown that restricting copper uptake prolongs the survival of patients with late-stage breast and kidney cancers.

Scientists in the lab of Michael Petris, a Bond Life Sciences Center principal investigator, have spent the last several years looking at this connection to try to figure out the specific requirement of copper in pathways that may contribute to cancer progression. Postdoctoral Fellow Vinit Shanbhag published research to that effect in the highly regarded scientific journal Proceedings of the National Academy of Sciences (PNAS) earlier this year.

His work aims to find a way to inhibit the enzyme family lysyl oxidase (LOX) to prevent the growth and spread of tumor cells. The lysyl oxidase (LOX) family of enzymes is a class of copper-dependent proteins involved in cancer progression.

“Blocking the delivery of copper to LOX family enzymes could be a powerful means to block LOX-mediated pathologies,” said Shanbhag.

To date, functional roles for LOX family members have been documented in breast, colorectal, prostate, gastric, hepatic, pancreatic and head and neck cancers, as well as cancers of the skin, including melanoma.

“In general, cancer has two important forms which are tumorigenesis and metastasis. Tumorigenesis is the formation of a primary tumor,” said Shanbhag. “It is easy to solve that problem because you can have surgery to remove a tumor, but if the tumor cells spread to different organs of the body, like during metastasis, that’s a serious problem.”

According to a study published by the National Center for Biotechnology Information, metastasis is responsible for roughly 90% of cancer deaths, an estimate that has changed very little in more than 50 years. Thus, scientists aim to prevent the spread of cancer cells to different organs.

The path to inactivating LOX family members starts with a gene dubbed ATP7A. The ATP7A protein plays an important role in moving copper in and between cells as well as regulating copper levels in the body. Shanbhag has discovered that blocking ATP7A function results in the inactivation of multiple LOX family members thereby inhibiting tumor growth and metastasis.

Shanbhag and his team first utilized CRISPR-Cas9 system to knockout ATP7A copper transporter gene in breast and lung cancer cells and demonstrated that cells lacking ATP7A have significantly reduced LOX activity relative to the wild type cells. His lab bench model of 4T1 breast and lung cancer cells looked at how the cells migrated after they are separated by scratching through the cells. Cells lacking ATP7A resulted in loss of LOX-dependent mechanisms of metastasis and had a defect in motility and did not migrate as well as compared to the wild type cells.

Next, Shanbhag and his team tested the tumor-forming and metastatic ability of the cells lacking ATP7A in mice models.

“The tumors formed by the cells lacking ATP7A were smaller, as compared to the big tumors that are formed by the wild type cells,” Shanbhag said. “The most significant part of the study was a reduction in the metastatic ability of the ATP7A deleted breast and lung cancer cells in tumor-bearing mice. We measured the metastatic nodules in the lungs of the tumor-bearing mice and found that there were higher numbers of wild type metastatic nodules relative to the significantly fewer number of nodules formed by the ATP7A deleted cells”.

Now Shanbhag’s and his collaborator’s attention has turned to whether ATP7A can be shut down in human cancers as a way to aid in treatment.

“Obviously you can’t delete the gene in humans because the ATP7A gene is important for other functions,” Shanbhag said. “The solution is a drug to block ATP7A function for a particular time period.”

The next step of his research is to find a drug that will block ATP7A’s function in humans.

“We have collaborated with Dr. Kamal Singh from Bond LSC to discover drugs that block ATP7A function. We’ve already discovered a compound we call MKV3. M stands for Michael Petris, K stands for Kamal Singh and V stands for Vinit.”

Although the researchers are in the process of testing the compound in animal models of cancer, it’s proven to be a potent blocker of ATP7A in cell-based experiments. The compound’s patent application is currently being reviewed by the University of Missouri.

“This drug could potentially be commercialized. Our goal is that the compound will function as well in the animal models as it does on the lab bench,” said Shanbhag. “Fingers crossed.”

This research was published on April 2, 2019 in the journal Proceedings of the National Academy of Sciences of the United States of America. Research contributors include Kimberly Jasmer, Sha Zhu, Adam L. Martin, Nikita Gudekar, Aslam Khan, Erik Ladomersky, Kamlendra Singh, Gary A. Weisman and Michael J. Petris