moberman’s Articles at WOW Fellowship Blog

Reflecting on my summer of research

In my last post, I mentioned that I would be conducting a major experiment seeking to elucidate the effect of our experimental compound on the efficacy of the existing neuroblastoma immunotherapy. My entire summer built up to this experiment, and I am thrilled to report that the results were largely positive. We were concerned that our experimental compound might interfere with the effectiveness of the existing immunotherapy, an antibody that modulates antibody-dependent cell-mediated cytotoxicity (among other immune processes) against tumor cells. Therefore, we were ecstatic to discover that the experimental compound actually appears to increase the efficacy of this process – at least in our simplified, in vitro ADCC model. Of course, as I have mused, research is rarely a linear path. Although we repeated this experiment twice more with the same results, the findings provoked new questions about our assay that will require future experimentation to affirm the validity of our conclusion. And, most importantly, we still need to assess how our experimental compound works with the immunotherapy in vivo, as live animals are far more complex than any in vitro model. Still, I am quite satisfied with my work, our findings, and how the summer wrapped up.

IMG_20160815_093037562 — Tumor cells that I maintained this summer in the incubator. As I’ve learned, in vitro models greatly simplify in vivo processes, which is both good and bad.

All in all, I do think I met my learning goals for the summer. I wanted to experience science in the “real world,” and this project, with its trials, challenges, and triumphs, definitely did just that. Participating in this project taught me how to transfer academic knowledge into a real-world context. I also wanted to learn more about biomedical research, as I am currently applying to veterinary school and am potentially interested in a career that combines clinical medicine and research. Participating in this internship opened my eyes to the world of research. I saw that even though research can be tedious and slow, it can also be incredibly exciting and fulfilling. This internship definitely piqued my interest in pursuing a career as a veterinary clinician-scientist.

IMG_20160812_121300985 — There is something thrilling about producing data that both answers questions and sparks new ones.

To other students interested in pursuing a similar internship, I would stress the importance of patience. For most of the summer, the research seemed very slow-going. I took about six weeks to become comfortable with the techniques and protocols and feel competent in the lab. At the same time, for many weeks we were attempting to utilize an assay that was not sensitive enough for our purposes, and running failing experiments over and over again was disheartening. However, this is all part of research and the learning curve; perseverance is definitely a vital quality in any researcher, especially one who is new to the field. Additionally, I would stress the necessity of keeping an organized notebook, as carefully writing up all of my experiments definitely made it easier to keep details straight as we progressed throughout the summer.

All in all, I am most proud of how much I was able to learn this summer: about neuroblastoma, immunotherapy, research, and my own ambitions.

Michelle Oberman ’16

Halfway Point: Learning from the Bumps in the Road

Since my first blog post, I’ve conducted twelve additional experiments, mainly working to optimize conditions for the big experiment that I will be conducting in about two weeks. I spent about six weeks attempting to optimize an LDH assay (which measures the amount of lactase dehydrogenase, a chemical produced in the endogenous metabolic pathways of all cells that is released when they lyse). My supervisor believed that this assay would be a good measure of immune system activity against tumor cells, as the immune cells would attack the tumor cells, causing the release of LDH. This assay also does not use any radioactive substances and so is safe and easy to handle. Unfortunately, we ultimately determined that the LDH assay was not sensitive enough for our purposes, and so we had to move back to the old, tried-and-true method that involves labeling cells with radioactive chromium. So far we’ve conducted a few different experiments using this method, and we were very happy to see that it has worked every time. As my supervisor remarked, sometimes the old way is the better way, even if it does mean working with radioactive isotopes. Now that we have a working assay, I will be conducting an experiment to see whether our experimental compound increases the immune cells’ ability to attack the neuroblastoma tumor cells. This experiment will be a big undertaking, involving about 15 hours of work, several different experimental groups, and numerous controls, so we are crossing our fingers that we will get the results we desire.

Setting up an LDH assay in the sterile hood

I am gaining confidence in my technical abilities, which was a major goal of mine before the summer began. Despite the fact that many of the experiments we ran had systematic errors, I’ve been able to learn a variety of research techniques through running these different experiments. I’ve become quite competent at cell culture, which is a heavily-utilized technique across the biomedical sciences. I’ve learned how to isolate immune system cells from rat spleens and whole human blood, as well how to prepare blood serum for analysis. Overall I’ve become more independent in the lab, in terms of planning and running experiments and analyzing data. Additionally, I’ve gained a deeper understanding of the scientific research process, as I’ve now seen that despite extensive planning, research is rarely linear; the twists and turns can nonetheless be valuable learning experiences.

wow blog — Another benefit of this internship: I’ve gotten good at Excel!

Since my internship is academic in nature, it has aligned nicely with my experiences at Brandeis. I’ve been able to apply some of the molecular biology and immunology knowledge that I’ve gained through my coursework at Brandeis. However, I’ve also seen that research, unlike school, is a collaborative effort so being able to work with a team is very important to the process. I’ve also seen that even when the theoretical concepts are clear, the logistics of planning and running experiments can be complex. This has shown me how the “real world” connects to the science that I learn in lecture; there is more to being a scientist than just having an academic understanding of science.

In conclusion, while the research itself has definitely felt slow-going at times, I am excited to test our experimental compound in a couple of weeks and am hopeful that the weeks of optimizing will pay off. Nonetheless, I have grown through this experience and have gained a good understanding of the research process, which has been informative to my career exploration of fields related to veterinary medicine.

Michelle Oberman, ’16

Week 1: An introduction to the art and science of cancer research

My own personal corner of the lab

I just finished the first week of my internship at UC San Diego’s School of Medicine. Thanks to my WOW fellowship, I’ll be here all summer helping to modify an existing treatment for neuroblastoma. According to the American Cancer Society, neuroblastoma is a cancer of the nerve cells that affects young children; it is the most prevalent form of cancer in babies [1]. As my supervisor explained to me on my first day of work, neuroblastoma is especially horrible because the current treatments are far from ideal. At present, there is a very high relapse rate in patients who have been “cured” of neuroblastoma; I was shocked to hear that there is a 60-70% failure rate from remission.

Check out this site for some heartbreaking, and hopeful, patient stories that humanize this horrible illness.

Once in remission, patients often receive an immunotherapy treatment called ch.14.18 (which, fun fact, was pioneered by my lab’s PI!). Ch.14.18 is an antibody that attacks the GD2 antigen present on neuroblastoma cells. However, I learned that a major problem is that the antigens are also present on nerve cells; therefore, this treatment is painful. Additionally, I was saddened to hear that even with the immunotherapy, there is a low 4-year survival rate at about only 55%. I will be conducting research to see whether adding an experimental compound to the ch.14.18 treatment improves its efficacy. While this may seem like a simple goal, testing this hypothesis will require numerous complex and time-consuming experiments, many of which have never been done before.

This week I conducted my first experiment. While I did not obtain great data, I learned a lot about the process of cancer research, which I am finding to be an art as much as an exact science. I was introduced to a variety of techniques I will be using throughout the summer, most importantly, cell culture. In order to conduct my experiments, I need tumor cells to treat, so this week I learned about maintaining human tumor cell lines in vitro (meaning, in the lab). Cells are quite finicky about the conditions they require for growth, and are also high maintenance, requiring new media every couple of days (a process known as “feeding”) as well as “splitting” when the growth becomes too dense. Check out this link for more information on cell culture.

I conducted a preliminary experiment looking at the effects of two different antibodies, as well as the experimental compound, on a human neuroblastoma cell line. Already on day two I was given the freedom to design my own experiment, as far as picking my controls and determining the concentrations of the compounds that I added to my cells. Today I collected and analyzed the data, which deviated from my expectations, so I will be re-doing the experiment next week. I learned an important lesson: research (often) doesn’t go as planned, and as a newbie, mistakes are practically unavoidable.

I’m excited to learn more about the research process this summer and to become adept at the techniques I’ve been introduced to. Also, as a pre-vet student, this internship provides an excellent opportunity to see how I like biomedical research, as lately I’ve been thinking about non-clinical aspects of veterinary medicine that might interest me. All in all, I am excited to forge ahead with my research and hopefully make my own small contribution to this very important field.

Source:

www.cancer.org/cancer/neuroblastoma/detailedguide/neuroblastoma-what-is-neuroblastoma

IMG_20160520_154358303 — Fact: a productive lab is a cluttered lab!

Michelle Oberman, ’16 (Dec)