Taking Care of the Small Stuff

Tigist Tamir, a third-year graduate student in the Major lab, was recently awarded the Howard Hughes Medical Institute’s Gilliam Fellowship to research cell-signaling mechanisms that could provide new targets for treating cancer.

As a kid growing up in Ethiopia, Tigist Tamir was interested in how things work. She recalls being a “ridiculous kid” who would break things around the house just to see if she could put them back together.

“It was always like that,” she remembers. “There were lots of kids who would gather items and try to make a radio. That was the coolest thing you could do. We did stuff like that a lot.”

Science was emphasized in her house growing up, but Tamir knew that there wouldn’t be many opportunities to pursue the subject in her home country after she graduated from high school, and at 16 years old, Tamir and her brother moved to northern Virginia, where their father lived.

The opportunities Tamir has found in the United States have included experience at the bench in a number of different labs and a variety of outreach efforts intended to promote diversity in the sciences.

Tamir was recently awarded the Gilliam Fellowship by the Howard Hughes Medical Institute to pursue research aimed at understanding how the protein kinase HIPK4 fits into the story of NRF2, a protein that has been associated with the progression of certain kinds of cancer.

Name: Tigist Tamir

Date of Birth: September 18, 1989

Hometown: Springfield, VA

Education: William and Mary, BS in Biology, BS in Biomathematics; PhD candidate in pharmacology at UNC

Research project: Characterizing kinases that regulate the transcription factor NRF2.

Extracurriculars: FEMMES Outreach day camp, Science Firsthand, DNA Day, Brain Awareness Week, organizer for the UNC Proteomics Interest Group

Hobbies: Tae kwon do

History

“I’ve always been interested in science. It’s always been my thing, and it was highly emphasized in our household, growing up and after we moved here. During undergrad, I studied math and biology.

“I was also able to get some basic research experience during undergrad. Part of my project was trying to figure out if a specific sex defect in the fruit fly ovary gives them male-specific characteristics. That’s the first time I learned about signaling, and there was also a lot of imaging and microscopy going on. The further I went into undergrad the more it reinforced my interest in doing research.

“In the summers after my junior and senior years, I participated in EXROP [the Exceptional Research Opportunity Program], a summer HHMI program that eventually led me to the Gilliam. I worked with Randall Moon’s lab [at the University of Washington] where we worked on Wnt signaling in colon cancer and melanoma. It was one of the first introductions for me into mammalian cell line research.

“After graduation, I also participated in the PREP program, which gives people the opportunity learn what is required of them in graduate course work. It was a more immersive experience than undergrad and gave me a different perspective on research.

“Through PREP I did research at the University of South Carolina’s School of Pharmacy in the lab of Dr. Michael Wyatt. It was more translational because it was dealing with chemotherapeutic drugs that have been used for decades and how they affect DNA damage response. It was a lot more molecular biology than I was used to. But it was also good for me to have that balance – going from protein to DNA, there was a lot of biochemistry for me to learn, so it helped me build a basis.

“By the time I started applying to graduate programs, I knew I wanted to do translational research but I also wanted to do something at the molecular level. Eventually that focused everything on biochemistry and molecular biology.”

Why UNC?

“Three of the many programs I applied to invited me back for an interview. What my decision came down to was not only did people here seem more relaxed, but I was looking for the program that was the best fit for all of my research interests and that was pharmacology at UNC.

“Channing [Der, PhD, Kenan Distinguished Professor of Pharmacology and member of the UNC Lineberger Comprehensive Cancer Center], was very informative about the culture here when I interviewed with him. He introduced me to a lot of faculty during the interview process and I was struck by how happy all the people were.

“And then, hanging out with the students, it was a lot more relaxed than other campuses I had visited. The night after my interview, hanging out with the students, was when I realized I could see myself here. It’s not that I didn’t have that moment elsewhere, it’s just that it felt more natural here.”

Why the Major lab?

“I rotated through some amazing labs and I wanted to be in all of them. I had to write down pros and cons lists and be objective about the decision.

“What it came down to for me was that I wanted to learn to stand on my own and to learn something new, and mass spectrometry was a black box for me at that time. Proteomics is a discipline that gaining more traction in Cancer Biology and I wanted to jump in it while I had the opportunity.

How did you get involved in diversity outreach at UNC?

“I went to Annandale High School in northern Virginia, which is one of the most diverse high schools in that area. I started taking a lot of the advanced science courses as soon as I came to the U.S. and I saw a lot more diversity in the hallways on the way to class than I did in the classroom. That struck a chord with me.

“It can be intimidating not to see a lot of people who look like you doing science so you get the impression that you might not be successful in it, but the truth of the matter is that there’s not enough integration. I think that’s especially true for students who are often categorized as being from underrepresented backgrounds. The best thing we can do for them is to show them that these opportunities exist.

“The Science Firsthand program was designed to be a day of immersive experience for high school students interested in science. I helped Josh [Hall, PhD, director of UNC PREP and Science Outreach at the UNC School of Medicine] organize it and we got a lot of volunteers from the different labs to give young people a chance to see what is behind what they assume is a closed door.”

Research?

“My project focuses on a protein called NRF2, which has been linked to resistance to therapy. Studies from UNC and other places have shown that there is a mutation in the pathway that leads to overexpression of this protein, especially in cancers.

“In order to find other therapeutic targets you have to find something that you can actually hit, but NRF2 has a protein half-life of like 20 minutes, so you don’t have a large window to target that protein. What I thought would be an interesting way to approach this problem is looking at kinases: ‘what are the kinases that are activating or deactivating NRF2?’

“So I did a screen overexpressing different kinases and using a luciferase reporter to identify if NRF2 was active or inactive. What I found was a handful of genes, or kinases, that were either activating or repressing NRF2. I eventually narrowed it down to six.

“Out of those, the one that I wrote about for HHMI was HIPK4.

“HIPK4 is a very understudied kinase, which provides a lot of avenues to pursue, especially as it relates to NRF2. Can we get ahead of NRF2 and control it if we target this separate pathway? So my project is heading in that direction – figuring out how HIPK4 contributes to the NRF2 story.”

What next?

“As far as the science side of things, I’m trying to establish relevance for HIPK4 in different kinds of cell lines, especially lung cancer cell lines, because that’s where I’d like my focus to be – NRF2 is highly active in a portion of lung cancer cases. From there, I’m beginning to work on drug screening to figure out which compounds we can use to either repress or activate NRF2.

“I’ve also been looking into what other proteins NRF2 regulates or is regulated by – that part is not well known – so one of my side projects with another lab member is to do a NRF2 interaction network. And that will hopefully provide more targets to investigate and more pathways to study.

“On the career side, I’ve been weighing my options. Being an investigator can be a hard road – not only do you have to get grants but you have to be innovative and exceptional in your science – but I’m ready to work to make it happen.

“Recently I’ve taken a step back from long term plans and decided to focus on the moment: once I graduate, I’ll want to get into a good postdoc program. In order to do that, I have to do awesome science right now, publish as much as I can, and stay involved in outreach programs.

“I’m definitely set on the principal investigator side of the career. I hope it happens. I will work to make it happen. That’s where I am: I take care of the little things here so that the big things eventually take care of themselves.”

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