Author Archives: Ulises

More Research to Come

I am very grateful to have been given this opportunity to participate in an enriching summer research program. BSURF has aided me in understanding more about the scientific world and how it works, as well as what are things that can be improved. I came into this program having a research background, but I have learned a lot more about research from participating in BSURF than I did before. Dr. Gayathri Devi helped me grow and become a better scientist and problem-solver. I appreciate my graduate student mentor Risa Gearhart-Serna for assisting me in this pathway of learning about science; she was extremely helpful in my research all summer. The relationships I formed with my peers inside and outside the lab are relationships that made me happy, and hopefully, they will continue to be a part of my life in the future.

I enjoyed the weekly seminars from different faulty members. Having scientists present their research and findings, and telling us about their science career pathways, was truly revolutionary. It came to show me that you never know where you might end up in life, no matter what goals you have set for yourself.

Lastly, I want to thank Dr. Grunwald and Jason Long for giving me the chance to participate in this program. Both work hard to keep the program running and ensuring we got the best out of this experience. They made this research experience possible for me and hopefully, they will continue impacting future participants.

Learning From Others

I have enjoyed the seminar component of this program since it has allowed me to meet many of the faculty here at Duke. These seminars have enlightened me of what makes Duke research so unique and how important it is to get involved in research at this university. I found it interesting to learn about the life pathways of these scientists and a common theme I have seen is that you never know where you might end up in life.

One of my favorite seminars was from Dr. Brian Coggins, Assistant Research Professor of Biochemistry. I was excited to learn about his research since the beginning of this fellowship because his research revolved around Biochemistry which is the area I plan to study while my time here at Duke. His work focused on NMR technology and furthering the potential of this technology. NMR is a topic that was covered in my Organic chemistry I class. I found it difficult to learn but once I started practicing NMR problems it became easier to understand. However, the class didn’t go into detail about why NMR is important and what implication it has in the real world. Learning about Dr. Coggins research gave me a greater insight in that field and allowed me to connect what I learned in class and apply it to ongoing research. Dr. Coggins research around NMR goes well beyond my scope of knowledge of the topic but I am interested to learn more about it once I start taking higher level chemistry courses.

A comment from Dr. Coggins that stuck with me was that he is never satisfied. It’s his curiosity that drives him forward and allows him to want to learn more. It is difficult to choose just one discipline and stick with it for the rest of your life. Dr. Coggins mention how he wishes to have more time to learn about other research since there are so many things fascinating out there. It is interesting to know that even Dr. Coggins, with his years of experience, still doesn’t know what will come next in his career, but his curiosity will certainly lead him in the right direction.

A Polycyclic Aromatic Hydrocarbon Environmental Chemical Mixture Increases Growth of Inflammatory Breast Cancer Tumor Emboli

Exposure to polycyclic aromatic hydrocarbon (PAH) chemicals is widespread due to their presence in emissions from tobacco smoke, wood stoves, and organic fuel burning throughout the world. Many PAHs are classified as carcinogens, and prior studies have shown an increase proliferation in an estrogen-receptor positive human breast adenocarcinoma cell line due to exposure to low doses of a complex PAH mixture. The objective of this study was to observe the effects of the same PAH chemical mixture on an aggressive human inflammatory breast cancer cell line using a 3D tumor emboli assay. We hypothesized that greater concentrations of PAH mixture would lead to greater tumor emboli growth. Cells were seeded in ultra-low attachment well plates and once emboli were formed, they were treated with different concentrations of PAH mixture, called Elizabeth River Sediment Extract (ERSE). Microscopic and statistical analysis revealed that low nanomolar doses of ERSE result in greater tumor emboli size compared to untreated emboli, in a dose-dependent manner. There was a positive correlation between emboli size and increased ERSE concentration, although a high micromolar ERSE dose was cytotoxic to the cells. Collectively, these results suggest that low-dose exposure to this PAH mixture can enhance growth of aggressive breast cancer cells, and may have a wider and more substantial impact on cancer progression and outcome.

Something Different Than Mines

This past week I have enjoyed listening to everyone’s research. Since all the fellows are in a lab conducting research most of the time, we don’t have that much time to talk about our research, so it was great learning about what others are doing. I enjoyed learning how some of the projects being conducted intertwine into mines and it made me rethink the way I am tackling my research project. I saw some interconnections between my research and others but I enjoyed Iris’s project since it is completely different than mines.

Iris Chang works in Dr. Dale Bass lab in the department of Biomedical Engineering. Iris main goal for her project is to uncover the mechanism of Traumatic Brain Injury (TBI), and discovering what causes such thing to occur. The two schools of thought for TBI is between linear and angular kinematics. Iris is more focus on exploring the role of rotational kinematics via the mechanism of shear shock waves. Studies have shown that injuries can send shock waves through the brain in an undesired direction which causes such tragic brain injury. However, how rotational acceleration works through shear waves is still not well understood.

The way she is tackling such project is by using a computer model that allows her to input rotational kinematics and analyze the strain in the model brain. Her second method is analyzing the damage done to the brain by conducting a pig brain impact testing. Her methods in her project involve methods I have never conducted and it is exciting knowing Iris is doing it. Her research made me wonder if the results from both methods be similar or will they differ? And if they differ, why? Can’t wait to hear Iris explain her lab’s data to us at the poster presentation in a few weeks. The best is yet to come.

Is Every Day the Same?

After completing my fourth week of the BSURF program, I have a better understanding of my role and what to expect in the lab. Most of my time in the lab revolves around a computer screen, while a small portion of my time is spent doing hands-on things. But my lab mentor tells me that thorough background research, careful planning of experiments, and careful data analysis take most of a bench scientist’s time, and not the actual bench work running the experiments. This ascertains that the best science possible is being done, to obtain data in a purposeful and hypothesis-driven manner.

With my project, there is a great emphasis in studying inflammatory breast cancer in an in vitro model. My time spent doing hands-on protocols revolve shadowing the graduate student, Risa, producing media for cells, cell culturing, splitting cells, and imaging the progression of tumor emboli via a microscope.

As mentioned earlier, most of my time is spent in front of the computer screen. I am in front of a screen because that is where the data is kept. Using computer software is how I can calculate the size of the tumor emboli growth quantitatively and use that information to produce graphs. However, graphs are tricky, because there are multiple of ways of interpreting the data depending on how you choose to represent and graph the data, and what you are comparing. Furthermore, what makes the process more complicated is finding the right way to convey the information to others, in order to produce a visual result that speaks to the postulates made during hypothesis formation. The foundation of science is built around discovery and sharing those discoveries with the public, and therefore the information scientists choose to share should be able to be understood by others, even sometimes intentionally by the general public. These past few days I have spent a lot of time ensuring that the way I chose to present my data is visually easy to understand and is able to get the point across that I am trying to make. There are some statistical analyses that we have done as well with the graphs to further speak to the significance of the results and trends we have identified from the data.

I am enjoying my time in the lab; I feel that I now understand more of the molecular and biological reasoning behind my project than I did in the beginning. Most of my days may be in front of a screen, but each day there are advancements in my project and I find out more about the data I have or find better ways to present my data to other people. What I have learned so far with this experience is that there is so much data on science projects out there, but it takes time to interpret it correctly. Hopefully, by the end of this program, I will be able to share my data in a way that is meaningful and easily related to my audience.

Drugs versus IBC: who will win?

Dr. Devi gave me some freedom during the beginning of the program to explore the work of other scientists in the lab to see what kind of research I would be interested in conducting. My interest lies in pharmacy; thus, I am interested in drug therapy and how certain diseases will react with certain drugs. I used my interest of pharmacy to design a project that suited my interest but at the same time would help the lab gain new knowledge.

One of the focuses of Dr. Devi’s lab is inflammatory breast cancer (IBC). IBC is a very aggressive form of breast cancer that forms no one solid tumor mass, but instead, forms characteristic diffuse tumor cell clusters which spread along the breast parenchyma and block lymph vessels. Furthermore, IBC is also known to affect minority populations and younger populations disproportionately and is thus an important health disparity issue. Polycyclic aromatic hydrocarbons (PAHs) are a class of chemicals emitted from incomplete organic fuel combustion, many of which are carcinogenic and linked to increased cancer risk at certain human exposure levels. In vitro studies with PAH chemical exposure in Dr. Devi’s lab have seen morphological and signaling pathway changes in breast cancer cells due to this exposure, wherein low-doses of PAHs can ultimately increase growth and survival of a panel of breast cancer cells.

The research I will be focusing on this summer is to validate the Devi lab 3D tumor emboli model for inflammatory breast cancer and to test the effects of an environmental chemical mixture on tumor emboli formation and/or pre-existing morphology using this model. Concurrent chemotherapeutic treatments may also be added in addition to this environmental chemical mixture to scratch the surface of understanding therapeutic resistance in these aggressive IBC emboli. The environmental chemical mixture is comprised of thirty-six PAHs characterized by mass spectrometry, and different concentrations of the mixture will be administered to an IBC cell line. Potential chemotherapeutic drug therapies to be used concurrently are U0126 (a lab-grade ERK inhibitor), Eloxatin (a topoisomerase inhibitor), and Trastuzumab/Herceptin (a HER2 inhibitor). These three different drugs all have different inhibition targets, but their overall goal is to restrict cancer cell proliferation and promote apoptosis. I can’t wait to see the results I will get from these experiments, and to share them with the BSRUF and Duke community.

Why do Science?

The Dr. Gayathri R. Devi lab revolves around translational and clinical applications of cell death signaling. Since this is a very broad topic, it allows Dr. Devi to take multiple avenues to conduct research. Her passion for research started as an undergraduate student in All India Institute of Medical Science (AIMS) located in New Delhi, India. There she had the opportunity to explore her options, and decided to pursue a science career. Her choice was between a practicing physician or clinical translational research. She decided to pursue clinical translational research because it allows for the bridging between both bench and bedside patient work. She felt that such type of work best fitted her personal qualities and her goals to help the scientific and public community. Clinical translational research allows for creativity; it allows you to be wrong, and even when you are wrong, you learn something new. It was with this form of thinking that Dr. Devi continued her career path and went on to receive her Masters in Biochemistry and her Ph.D. in both Biochemistry and Molecular Biology from the University of Nebraska Medical Center.

Dr. Devi discovered the insulin-like growth factor (IGF) binding domain during her time under a Nebraska Research Initiative Biotechnology Fellowship. This discovery led her to her postdoctoral fellowship at the Oregon Health and Sciences University, where she studied growth factors and prostate cancer. After years of research and hard work, she transitioned to a position at Duke University in 2005. Her time at Duke has been amazing in her perspective. She enjoys interacting not only with postdoctoral associates and graduate students, but also with undergraduate students. She truly believes that her work goes beyond just doing research on inflammatory breast cancer, but also incorporates training the next generation of scientist and creating a community between all participants in the lab where everyone learns from each other. As mentioned previously, being wrong is still learning, and there is always opportunity in this. Dr. Devi once challenged a grad student working in her lab on the ability of a protein, X-linked inhibitor of apoptosis protein (XIAP), to increase tumor growth of IBC. Both had a different hypothesis regarding the protein, but the graduate hypothesis was correct in that XIAP played a role in apoptosis and tumor growth. Dr. Devi’s lab thus moved forward and learned more about IBC, and such discovery has allowed her research to continue to grow.

Dr. Devi has had many people to keep her lab running over the years, including a graduate student who joined last year, named Risa Gearhart-Serna. Risa is my lab mentor and has answered many of my questions and aided me in the research I’ve done so far in this program. Risa went to Mills College and got her bachelor’s degrees in biology and environmental studies. Her life career goal is to do good science, science that will benefit the world, science that will help us learn more about cancer and ways to treat it. She enjoys the collaborative aspect of science that some overlook, having people around you that can help you and who you can learn from. That is what makes this type of career path enjoyable for her.

Both Dr. Devi and Risa are great mentors. Both have their own goals to help the science community, and they both have unique characteristics that make them enjoyable to be around. Hopefully with this summer experience I can learn from them, because they both have amazing things to offer.

Many Ways to Study IBC

I came into the program with enthusiasm, I was excited in the sense that I would be able to continue doing research which is something I was unable to do during my first year at Duke. I was lucky enough to get into Dr. Devi’s lab which is centered in studying inflammatory breast cancer (IBC). With any research experience, there is background reading that must be done to have a good understanding of the project you might be working on. The papers I’ve read were fascinating, they revolved around different proteins that have been identified to help IBC cells, the difficulties in treating IBC, and different environmental factors that may aid IBC cell growth. Reading research articles are never easy, new content is thrown at you but over the week by asking questions and rereading the articles, I now have a greater understanding than I did before.

Not only did I read research articles but I also shadowed other staff members working in Dr. Devi lab which is Ph.D. student, Risa Gearhart, and Dr. Xuhui Bao. I shadowed Risa cell culture SUM149, which is the cancer cell lines we are using to experiment on IBC. Furthermore, she counted the cells of the culture she created via a microscope and cell seeded them. The culture she created was treated with different concentration of polycyclic aromatic hydrocarbons (PAH) which will be used for tumor emboli experiments. Unfortunately, there was a computer malfunction that occurred which enable us from imaging the process of the tumor emboli, so this experiment will be redone next week. Risa is also continuing a previous experiment which involves the usage of western blot development on MDAMB231 cells which is another procedure I saw her perform.

Dr. Bao is still focused on IBC but one of his experiments is centered on in vitro mice models. On Thursday, he showed me the mice that were being tested on and the window chambers that were placed on them to allow him to see the progression of the IBC throughout the lymphatic system via a microscope. Unlike other breast cancers, IBC forms no one solid tumor mass but instead forms characteristic diffuse tumor cell clusters. Therefore, he is imaging the spread of these IBC clusters on mice to better understand the flow of these clusters and what allows such cancer to do so.

Since there was a computer malfunction, I have spent some of my time writing up an introduction to my project and gathering results from experiments done in the past. The first half of my introduction focuses on giving readers an understanding of what IBC is, it’s unique characteristics and findings that Dr. Devi’s lab has made in the past. I am excited to see what project I will be working on this summer, Dr. Devi has given me the freedom this week to explore different aspects of her lab and see which project I will be interested in working on. Since my interest lies in pharmacy, I have been considering doing more research on IBC and DSF-Cu, or testing different treatments on IBC and seeing the effects that certain treatments will cause. Again, I’m excited for the work I will be doing, and I’m eager to see where my project goes.