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CAR-T from A to Z

Often touted as a “miracle therapy” for certain cancers, CAR-T treatment has created a lot of buzz in the immuno-oncology field. There are over a hundred CAR-T clinical trials open in the U.S. and the first commercial CAR-T could possibly be approved by the end of this year. Initially, the introduction of the therapy in 2012 had some warranted safety concerns. The technology is inherently aggressive and can become unruly if not it’s not properly monitored. For this reason, the first clinical trials of CAR-T created damaging side effects and in some cases the therapy was associated with patient deaths. However, therapy design has been revamped over the past five years and researchers are finding ways to dampen the level of toxicity the therapy produces. Despite the risks associated with CAR-T, clinical trials have shown to be effective at treating the targeted cancer. Recently, clinical trials have shown remission rates of up to 94% and as a result the therapy has attracted millions of dollars from investors. Although the technology is not perfect, there is optimism in the field that CAR-T can radically improve cancer patient care.

CAR-T treatment involves the infusion of transgenic T-cells that express a Chimeric Antigen Receptor (CAR) on their cell membrane into the patient. The most common procedure involves isolation of the patient’s own T-cells, which are then genetically modified and expanded in vitro. These transgenic T-cells are then infused back into the patient to specifically target tumor cells. The CAR-T receptor of the transgenic T-cell contains three domains: (1) a target-binding domain externally exposed to the extracellular environment, (2) a transmembrane domain, and (3) an activation domain that is intracellularly contained.

The target-binding domain is engineered to be structurally different than endogenous T-cell receptors because it recognizes antigens that are independent of major histocompatibility complex (MHC) antigens. Instead, CAR-T recognizes antigens that are either proteins, carbohydrates, or gangliosides on the tumor cell surface. The transmembrane and activation domains of the CAR-T receptor are responsible for activating and triggering T-cell proliferation when the receptor binds to its target antigen. When activated, the T-cells mediate killing of tumor cells by two mechanisms: (1) secretion of granzymes and (2) activation of death receptor signaling in the tumor cell. These killing strategies are potentiated by additional signaling receptors on the T-cells that can improve T-cell proliferation and cytokine release. As of now, research teams have designed third-generation CAR-Ts that contain costimulatory receptors that ameliorate antitumor activity and proinflammatory cytokine secretion.

The high success rate of CAR-T therapy in clinical trials has prompted several companies to compete for commercialization and introduction of the therapy into the market. At the moment, Novartis is leading in the race of clinical development and commercialization. In November, the company successfully completed Phase II trial of the CAR-T candidate for B-cell acute lymphoblastic leukemia (ALL). Novartis is currently preparing to submit applications to the FDA this year. Kite Pharma also recently completed their Phase II clinical trials for CAR-T therapy against lymphoma and has also submitted regulatory applications with the FDA. The progress made by these companies has created a great amount of excitement around their respective CAR-T therapies. However, some researchers are skeptical that FDA approval will be granted for the therapy. Severe side effects still exist and deaths have been reported in some clinical trials. Juno Therapeutics, a company that was initially in the stiff CAR-T race, terminated their clinical trial after 5 patients died of cerebral edema caused by the therapy. Some pharmaceuticals have  taken steps to mitigate harmful CAR-T side effects. For example, Cellectis has developed a CAR-T therapy with a switch control system that only activates the transgenic T-cells when rampamycin is present. This therapy is currently in Phase I clinical trails and has already shown a lot of promise after saving two infants from leukemia. Similarly, Bellicum Pharmaceuticals is developing a technology that requires rimiducid to be present for CAR T-cell activation.

A technical limitation of CAR-T technology is that it is challenging for CAR T-cells to target solid tumors. At the moment, the therapy is most effective against hematological (blood) cancers but not solid tumors. To solve this problem, the biopharmaceutical Celyad is developing a CAR-T that expresses Natural Killer Receptors (NKR) that can bind ligands of solid tumors. The company is currently beginning clinical trials with these NKR-expressing CAR-Ts. Researchers have also suggested combining checkpoint inhibitor drugs such as PD-1 with CAR-T therapy as a multi-pronged method to attack solid tumors; however the side effects of this combination therapy are currently unknown.

From a patient’s  point of view, another limitation of CAR-T therapy is that it is an expensive and lengthy process because CAR-Ts are developed from the patient’s own cells. Cellectis and Celyad are offering a solution to this problem by developing an allogeneic CAR-T therapy—that is, the T-cells are derived from a healthy donor and are immediately available when they are needed. This technology is still at its early stages and is scientifically challenging to develop since foreign donor T-cells can be readily attacked by the patient’s immune system. Additionally, the manufacturing, transportation, and banking of the allogenic CAR-T would also prove to be tricky.

The plethora of different CAR-Ts in clinical trials has given hope to patients and physicians that the therapy will be introduced to the market fairly soon. Although a few limitations exist for CAR-T, ongoing research and clinical development continues to refine the therapy and encourage the public that CAR-T has the potential to transform the immuno-oncology field.

References

  1. Yu et al. Journal of Hematology & Oncology(2017) 10:78
  2. Fernandez, C. (2017, January 16). A Cure for Cancer? How CAR-T Therapy is Revolutionizing Oncology. Retrieved from http://labiotech.eu/car-t-therapy-cancer-review/
  3. Harris, D. (2016, December 15). Opinion: Balancing Risks and Rewards of CAR T-Cell Therapy. Retrieved from https://www.the-scientist.com/news-opinion/opinion-balancing-risks-and-rewards-of-car-t-cell-therapy-32352
  4. Bock, E. (2016, November 18). CAR T-Cell Therapy Moves Closer to FDA Approval. Retrieved from https://nihrecord.nih.gov/newsletters/2016/11_18_2016/story1.htm
  5. Keshavan, M. (2016, August 23). Experimental cancer therapy holds great promise—but at great cost. Retrieved from https://www.statnews.com/2016/08/23/cancer-car-t-side-effects/
  6. Brower, V. (2015, April 1). The CAR T-Cell Race. Retrieved from http://www.the-scientist.com/?articles.view/articleNo/42462/title/The-CAR-T-Cell-Race/

GSC COMMITTEE & CLUB UPDATES: MARCH 2016

GSC Career Paths Committee

On February 13, 2017, the GSC Career Path’s Committee kicked off the year with a workshop learning the basics of the Prism Graphpad software. In the past, students had expressed interest in analysis of data using statistical software as well as graphing the data in a presentable fashion. Therefore, the GSC thought a workshop on PRISM would not only be very useful but also have a significant impact on the students’ research careers. The workshop was kindly guided by Dr. Dan Cox, a professor in the Neuroscience department, and it took place in the computer room in the Sackler library. The workshop was well-received, according to GSC representatives Vaughn Youngblood and Roaya Alqurashi. “(The workshop) was a successful one. The attendees loved how Dr. Cox explained each application you will need to use in Prism with an active learning experience” Roaya said. Vaughn mentioned “the Prism workshop was helpful!  It taught the fundamentals of using Prism along with how to represent different types of data.  Hopefully, we can bring Dr. Cox in for another session with another statistical program like R.” If time permits this year, the GSC Career Path’s Committee hopes to hold several more workshops like this with different analysis softwares (R, SAS, etc.).

Opposites Attract: The Unlikely Marriage of Science & Fiction

Science, as a subject of study, often comes into conflict with other ways of thinking about the world. Religion. Philosophy. Art. The caricature of science as an opponent to these ‘humanitarian’ endeavors obscures the real relationship: symbiotic. In the case of science and literature, science provides fiction with an intriguing playground to muck around in, while fiction gives science a more human voice. This give-and-take between the two is what makes the genre of science fiction so rich, so enduring, and above all, so entertaining.

Science fiction more often than not uses science as a tool to explore other subject areas versus the science itself. It is not the engineering of the 20,000 Leagues submarine or the bioelectricity behind the monster in Frankenstein that makes these books long-standing members of high school reading lists. Readers are not likely spellbound by Margaret Atwood’s MaddAddam series mainly because of the intricacies of the genetic engineering catastrophe that ended her version of our world. No one likes Star Wars because of its explanations of the physics behind inter-galaxy travel. Fiction is not a mirror that reflects science to readers so that they can understand its most basic aspects. Instead, fiction is a prism that refracts science, fractioning and expanding it into its ripple effects and societal implications. It bends the bleached starkness of the discipline into a million different shades, spattering dark implications and bright hope for humanity in equal measure.

It is not always a fair coloring. Dystopia walks hand-in-hand with science fiction more times than not. Those stories do speak well of the perseverance of the human condition but often at the cost of vilifying some aspect of science. (Everything becomes a villain if left unchecked long enough, after all.) Still, fiction doesn’t just take from science; it gives as well. Science fiction is always ahead of its time, more audacious in imagining what human hands are capable of creating than what we believe is achievable at the time. With that creative inspiration, our history has shown it is inevitable that science fiction becomes science fact, from endeavours as incredible as space travel to tools as mundane as credit cards. And as such, science fiction has the privilege of not just asking can we, but also should we, and it has the added advantage of most times asking it first.

The audacious pushing of boundaries beyond the confines of the contemporary scientific knowledge within science fiction also creates a unique and rich environment for rebellion. Because in that type of story, in an imagined world that both is and is not this real one, what else could be different? Who else could become something more than what they are, or what society tells them they are?

This type of rebellion is what led to the existence of the genre itself. In 1666, the English duchess Margaret Cavendish published The Blazing World, a prose piece often considered one of the first utopian fictions and the precursor to ‘science fiction’ (a term not officially coined until 1926) as we know it today. Cavendish was an anomaly of her time, publishing plays, essays, and prose that tackled philosophy, rhetoric, and fiction, all under her own name instead of anonymously. She also was the first woman to attend a meeting of the Royal Society of London, despite fierce protest, and did not hold back in commenting on and even criticizing the scientific presentations and practices she observed. Her novel dove into discussions tackled by male authors of the time period–the conflict between imagination and reason or philosophy and fiction–but also was groundbreaking in two ways. First, she explored these topical areas within an alternate universe entirely of her own making but one that still used contemporary science of the era; second, her story strikingly centered on herself as the main character, where she traveled in between the two worlds. In a time where women were not considered capable of studying complex topics such as science, the Duchess of Newcastle used her writing to boldly carve herself a space in which she could defy that notion. In the process, she wrote into existence the first examples of many science fiction tropes still widely used today.

Her actions paved the way for other rebels, such as Mary Shelley, the mother of the first science fiction horror novel, Frankenstein. While a grey, depressing summer and a writing challenge born out of boredom provided an opportunity to craft her terror-filled story, her imagination was ultimately sparked after a firelit evening conversation with the controversial Lord Byron about what life is and how to create it. Despite being supported in her endeavours by her companions and her husband, Shelley ran into criticism upon publishing her work–incidentally most strongly from the specific publishers who knew the author was a woman–because it challenged the entrenched ideology of God being the only conceivable creator, not Man (or, in her case, Woman). In the deeply religious society of Victorian England, this was a revolutionary act.

Cavendish and Shelley may have been the some of the first authors to use sciene in fiction to challenge the social and moral status quo, but it was a tradition that persisted in the genre throughout the twentieth century. Starting in the 1960s, female authors were among the first to interrogate the definitions, implications, and biases associated with gender, class, and race. Ursula Le Guin’s sci-fi novel The Left Hand of Darkness–with its gender-fluid alien race dissecting what exactly gender and sex means outside of its Western civilization confines–led the charge. This breakthrough was followed by Joanna Russ’ 1975 matriarchal parallel-universes utopian novel The Female Man, then by Octavia Butler (who was the only African-American woman publishing in the genre at the time) and her late-1980s space trilogy Xenogenesis which explored race in addition to sexuality.

These revolutionary works also represent a broader theme within the genre: the influence of contemporary events of the era in which they were written. Science fiction is as much a reflection on the scientific knowledge of the day–and what could come of it–as it is on the historical and political backdrop of the time. Many early science fiction novels from the eighteenth and nineteenth centuries focus on stories of exploration and the technology that allows journeys into lands unknown. Most notable of these are Gulliver’s Travels (Jonathan Swift, 1726), 20,000 Leagues Under the Sea (Jules Verne, 1870), and The Time Machine (H.G. Wells, 1895). Historically, these centuries were flooded with exploration expeditions by European countries, and later the United States and Russia. While discovery for political and economic gain was the main purpose of most 18th century explorations, those carried out in the 19th century were more focused on deepening knowledge of the world, often through scientific observation and analysis. So, it is little wonder that the science fiction of the era reflected that desire to know more about the surrounding environments.

In the early 20th century, the domination of exploration themes in science fiction gave way to playing around in other subject matters–such as technology, biology, and medicine–which would later become genre staples. The early half of the century was one of rapid scientific advancement as much as it was political upheaval, and the collision of these two jarring phenomenons is reflected in the science fiction of the day. It was during this era that some of the seminal works of the genre were produced, including the post-Bolshevik revolution novel We (Yevgeny Zamyatin, 1924) and the science fiction classics Brave New World (Aldous Huxley, 1932) and 1984 (George Orwell, 1949). These novels each address how uncurbed scientific advances lead to a dystopian political society, and their thematic commonality clearly demonstrates the lasting impact several world wars and fast-paced science had on the public psyche of the time.

While dystopia strongly persisted within science fiction in the middle of the 20th century, the worlds crafted within genre novels did begin to grow a little less dire. As technological development continued to accelerate and started infiltrating daily life in the Western world–thus ‘normalizing’ it–likewise did the role of technology grow in fiction as androids and robots appeared on the genre scene. Authors of the time such as Isaac Asimov and Philip Dick couldn’t help but ask–and then answer through their writing–questions pertaining to the human condition in relation to the (imagined) creation and existence of non-human life. This philosophical bent echoed the early origins of the genre, going all the way back to Cavendish’s precursor work, demonstrating how far the genre had progressed.

Glancing back and paying homage is all well and good, but science fiction also found new ways to move forward at the end of the 20th century. In 1979, The Hitchhiker’s Guide to the Galaxy added a little laughter and good humor to the genre, breaking ground for many others to follow across even until today. The gloom of the war-torn early decades also seemed to have worn off, with a revitalization of the previously ‘tired’ utopian sci-fi tradition by Kim Stanley’s Mars trilogy in the 1990s. This trend of revitalizing and redefining the genre has persisted into recent years, with the semantic alteration by Margaret Atwood, who calls her novels not ‘science’ fiction, but speculative fiction. In her MaddAddam series, she reaches for what might be just possible in the realm of science and society, instead of the complete impossible. In some ways, this approach brings about an even more imaginative (and frightening, and wonderful) vision of what the human mind can create when challenged in the perfectly right and wrong ways.

Ultimately, the fiction of science is as elusive and ever-changing as the real thing. It circles itself: thought and action, can and should, might and will and have done. Whether we as scientists today use science fiction as inspiration–or as a warning–only time will tell.

Humans of Sackler: Nafis Hasan, “I Refused Determinism”

Humans of Sackler, 30 January 2017

Nafis Hasan, Cell, Molecular & Developmental Biology, Fourth-Year Student: “I Refused Determinism”

This month I present, for your reading pleasure, excerpts from my interview with Nafis Hasan from CMDB. Nafis and I had a remarkably wide-ranging conversation covering existential philosophy, cultural differences between Bangladesh and the US, the exquisite symmetry between ecology and cell biology, and current controversies in carcinogenesis research. I can only hope to capture in the space below a mere whisper of his deeply-considered intellectual convictions and passion for social justice. Fortunately, Nafis has also authored an editorial on Science Activism in this very issue, and I strongly urge you, dear reader, to check that out next!

 

Having a grand time in Dhaka
Having a grand time in Dhaka

AH: Where did you grow up?

NH: I grew up in the house that my father and his brothers built in Dhaka, Bangladesh, and moved to the U.S. when I was 18. Most of my dad’s siblings and their families lived with us in Dhaka. As kids, we didn’t really have the notion of “privacy” for the longest time: the elders would each get a room and the kids would sleep in the living room on a big mattress. My cousins and I would all get into trouble at the same time… it was fun!

 

On the road with college friends
On the road with college friends

AH: Have you had any opportunities to travel around the States?

NH: For F1 visa (student visa) holders, you have a 3-month window where you have to find a job or get into school. After graduating from Lafayette College [in Easton, Pennsylvania], I thought, “If I have to leave the country, I might as well see it.” So when one of my friends said, “Let’s do a road trip,” I said “Let’s do it!” We started from Pennsylvania, went down to Virginia, our first stop was Shenandoah – I had actually never been camping before that, it was all a very new experience. We had two American kids, a Colombian kid, and a kid from South Africa… It was very liberating, and I started to see the country as it really is. At the same time, on the road, I was interviewing for jobs. I remember doing a job interview [by video phone] at a McDonalds in Idaho. I borrowed a shirt from one of my friends who dresses nicer than I do, since the interviewer could only see the top half of me… Over the course of two months, I think I applied to 200 jobs. Finally, I ended up getting a research tech job at Thomas Jefferson University in Philly.

 

Basking in the beauty of nature at Yellowstone
Basking in the beauty of nature at Yellowstone

AH: What was it like adjusting to American culture?

NH: When I came to America, I had no idea what to expect, I had only heard things from my cousins who came here for college and what was on TV. One thing that I had in my mind was that I was going to try and meet as many people of different nationalities as I can. But there was a big cultural divide, how they grew up versus how I grew up. I think the road trip really helped me to understand the diversity of American people and especially during these times when people are so polarized, I reach out to that experience. We grew up seeing this version of America as the land of opportunity, the land of freedom, but America is not the government, is not their foreign policy, is not the consumerism that has taken over the world… America is more about the people that you meet here, and that’s how I see the country. America encapsulates the dichotomy of homogeneity versus heterogeneity, and I think that’s so beautiful.

 

The scholar/activist as a young man
The scholar/activist as a young man

AH: When did you begin to discover your interest in biology research?

NH: In Bangladesh I went to a private school that taught everything in English. The division of sciences starts in 7th grade, and biology was definitely the most interesting to me. At the same time, I was caught up in the process of deconstructing my religious identity, because I was reading biology which has hard facts about how your body works, which calls into question how life was created… I found that more fascinating than having a set answer imposed by some superior being.

 

Positive work environment!
Positive work environment!

AH: How did you choose your field of study for grad school, and why is it so interesting?

NH: I started reading a lot of scientific nonfiction, presenting cancer as a very complex biological phenomenon, which was fascinating to me. I also had a solid foundation in breast cancer by the time I applied for grad school and I wanted to pursue that… I had seen lots of tumors, but no mammary glands. The more I learn about the mammary gland, the more I am fascinated by it. It develops throughout life: initially it’s just a branched structure that looks like sticks; when you get pregnant, it almost flowers, with grape-like clusters that come up through alveologenesis and these alveoli then revert back to the branched structure after weaning. It’s comparable to how trees shed leaves in the Fall, except in reverse: this course of nature – the seasons that you see – the same dynamic is there in animal tissue. And all of this is happening through the lifetime, after the majority of the organs are already fully developed!

 

100 miles?!
First Century – Repping Sackler at 2015 Tufts Century Ride

AH: What is one of the big challenges or controversies in your field at the moment?

NH: Traditionally, cell culture is done in two dimensions, on plates that are usually plastic – and plastic is not a natural substrate for cells to grow on, so you can’t recapitulate the same 3D environment where the cells are growing inside an organism. You can either try to mimic the natural environment as much as possible, or try to make a scaffold that is biocompatible… Cells need to be able to manipulate their environment, just as the environment should be able to provide them with physical or chemical cues to make them grow or organize in certain ways. Our lab has a very organic approach to it: we do 3D cultures in type 1 collagen, the predominant structural protein found in the mammary gland stroma. We believe that “organicism is greater than reductionism.” This is where we’re at odds with a lot of others in the cancer field, where reductionism is still the predominant philosophy. And we’re not saying it’s bad! It’s just insufficient to explain carcinogenesis.

Notes from Up North: What is an IDeA COBRE?

By Lucy Liaw, PhD Tufts/MMCRI

Here at Maine Medical Center Research Institute, we are very happy to be supporting Tufts trainees and working with many Tufts investigators here and in Boston to provide core facility services such as transgenic mouse generation.

Did you know that many of our core facilities were established at Maine Medical Center through a special NIH program, the Institutional Development Award (IDeA) Program? The IDeA program was established by Congressional mandate in 1993 to help develop research infrastructure to support biomedical research in 23 states that historically have had a low level of NIH funding. Maine is one of those states. In fact, there was a time when 50% of NIH funding went to researchers in 5 states (Massachusetts being one of those heavily funded states!), while the 23 IDeA eligible states together only received about 5% of all NIH funds. Over the last 23 years, NIH investment in biomedical research in Maine has contributed to a burgeoning biotech scene (http://www.mainebioscience.org/access_resources/bioscience-map-of-maine/) and a highly collaborative network of research institutes.

One of the components of the IDeA program is the Centers of Biomedical Research Excellence (COBRE). Maine Medical Center has been fortunate to have received two COBRE awards since 2000, one with the theme of Vascular Biology, and one in Stem and Progenitor Cell Biology. These awards have supported the recruitment of new junior investigators to Maine Medical Center (with appointments at Tufts University School of Medicine), and also the establishment and expansion of our core facilities.  Please visit our website at mmcri.org, and find “Core Facilities” under “Research Services & Resources” to see if we provide services that could be useful to your research!

Microinjection of mouse fertilized oocyte. Our Mouse Transgenic Facility performs genome modification using standard transgenesis, gene targeting in ES cells, or CRISPR/Cas. In 2017, we will start to offer services for CRISPR/Cas project design and sgRNA synthesis.
Microinjection of mouse fertilized oocyte. Our Mouse Transgenic Facility performs genome modification using standard transgenesis, gene targeting in ES cells, or CRISPR/Cas. In 2017, we will start to offer services for CRISPR/Cas project design and sgRNA synthesis.

 

Imaging by microCT. We run a Scanco vivaCT40 for microCT imaging of bone, teeth, fat, and the vasculature. Image, above right, shows microfil perfusion of the vasculature of a tumor xenograft, used to quantify and measure tumor angiogenesis.
Imaging by microCT. We run a Scanco vivaCT40 for microCT imaging of bone, teeth, fat, and the vasculature. Image, above right, shows microfil perfusion of the vasculature of a tumor xenograft, used to quantify and measure tumor angiogenesis.

 

Proteomics and Lipidomics Core Facility. We run a mass spectrometry resource with state-of-the-art protein and lipid profiling capacity. Recent studies include experiments to study tissues including adipose tissues and the skeleton, and how their protein and lipid content changes during metabolic disease.
Proteomics and Lipidomics Core Facility. We run a mass spectrometry resource with state-of-the-art protein and lipid profiling capacity. Recent studies include experiments to study tissues including adipose tissues and the skeleton, and how their protein and lipid content changes during metabolic disease.

 

Histopathology Core Facility. We provide full services for tissue processing, embedding, sectioning, routine histology, and immunostaining. We work closely with our Maine Medical Center Biobank to generate tissue arrays for screening of human disease specimens from patients.
Histopathology Core Facility. We provide full services for tissue processing, embedding, sectioning, routine histology, and immunostaining. We work closely with our Maine Medical Center Biobank to generate tissue arrays for screening of human disease specimens from patients.

GSC Committee & Club Updates: November 2016

Tufts Biomedical Queer Alliance (TBQA)

by Laura DarniederNRSC, Amanda GrossPPET

TBQA-oSTEM Joint Networking Mixer and Panel
We are having our TBQA-oSTEM Joint Networking Mixer and Panel on Friday, 11/18 from 6:00-8:00pm in the Crane Room on the Medford Campus. Food will be provided!

TBQA Transgender Health PanelDecember 1, 3pm, Sackler Auditorium

The Tufts Biomedical Queer Alliance (TBQA) invites you to come learn about the current state of transgender healthcare. We are pleased to welcome Dr. Anne Koch, DMD, to share her personal experiences of the healthcare system as both a patient and provider. A professional panel composed of Dr. Julie Thompson (Primary Care, Fenway Health); Dr. Stephanie Roberts (Endocrinology, Boston Children’s Hospital); and Cei Lambert (Trans Patient Advocate, Fenway Health) will join Dr. Koch in a panel discussion of the services they provide from both medical and social perspectives. A complimentary reception will follow.

Please register at: https://goo.gl/sCCmbT


Tufts Biomedical Business Club (TBBC)

from Aaron BernsteinCMP

Upcoming Events

TBBC Case Study Group – Mondays — 5-7PM, Jaharis 508

Practice solving cases, gain insight and tips, and learn more about the field of consulting.

TBBC Tufts Biomedical Data Science Club: Information Session – Tu Nov 29 — Time and location TBA

The Tufts Biomedical Data Science Club is a resource for students wishing to learn and apply programming techniques in order to tackle big data problems in the biomedical sciences. No programming experience required! The club hosts bi-monthly meetings, works on group projects, and provides opportunities to hear invited speakers and network with others interested in big data. Please email Matt Kelley at matt.kelley@tufts.edu with any questions.

TBBC Seminar Series: Liz O’Day, Founder and CEO of Claris Therapeutics – Tu Dec 6 — 5:30PM, Sackler 216A

Olaris is a venture-backed drug discovery company that uses a proprietary NMR-metabolite profiling platform to unlock aspects of human metabolism that could never before be analyzed. Focusing on diseases with limited to no treatment options, Olaris uses their technology to uncover previously unknown biomarkers and molecular targets to develop breakthrough therapies that fundamentally alter how these diseases are diagnosed and treated.

TBBC Consulting Seminar Series: Peter Bak, PhD – Tu Dec 13 — 5:30-7:30 PM, Sackler 221

Join us for a discussion with Peter Bak, Manager at Back Bay Life Science Advisors. Dr. Bak will talk about transitioning from a PhD program to life sciences consulting and career opportunities at BBLSA.

Recent Events

TBBC Health Advances presents, “Diagnostics Commercialization Challenges”

Th Oct 6: TBBC hosted Sackler alum and Partner at Health Advances, Dr. Donna Hochberg (SK03), who discussed the career path that led her from the bench to her current role as the leader of the firm’s Diagnostics and Life Science Tools Practice. She also led the group through a business case study exploring the challenges of bringing diagnostics to market. 

TBBC Biotech Buzz with Hannah Mamuszka

F Oct 21: Hannah Mamuszka, picked by Future of Biopharma as one of 5 women to watch in Boston, and founder and CEO of Alva10, a company specializing in precision medicine, joined us for an informal conversation about the future of diagnostics, the latest news in biotech, her career, and Alva10. 

TBBC, GSC, and the Sackler Dean’s Office Career Exploration Panel

Th Nov 3: A panel of senior graduate students provided insight about steps that newer students can take to prepare themselves for a variety of career paths, including: academic/industry science, teaching, entrepreneurship, science communication, policy, data science, venture capital, and consulting. (For a more in-depth recap, read the Insight article here!)


Tufts Mentoring Circles (TMC)

from Daniel WongCMP

This year, the graduate student and post-doc mentoring circle programs have merged together to form a larger, single Tufts Mentoring Circles program that started for the 2016-2017 academic year with a kick-off event on Thursday, October 6. In total, 71 people are participating in the Mentoring Circles program this year: 24 mentors, 21 graduate students, and 26 post-docs between the Boston and Medford campuses. These mentors, who are faculty, post-docs, senior graduate students, and industry and non-traditional professionals working in different fields, will be working in pairs to advise and facilitate discussions with small groups of post-doc and graduate student mentees over the course of this year.  Mentors and mentees were matched together based on their personal and professional development interests indicated in the registration survey that was available online in September. Each group, or circle, will meet monthly on their own schedules to have discussions as they see fit on topics they choose. A closing event will be held toward the end of the academic year, likely in May or June 2017. Registration is now closed for the year, but for more information and to be notified when registration opens next year, contact us at tuftsmentoring@gmail.com.

The graduate student-focused Tufts Mentoring Circles program was founded in November 2014 through the Sackler GSC as a peer mentoring program to serve the professional and personal development needs of graduate students, and also facilitate inter-program and -department communication and collaboration. Tufts Mentoring Circles is based on the Association for Women in Science (AWIS) Mentoring Circles program.

ICYMI: Career Exploration Panel

In this month’s edition of ICYMI, I’ll be giving you the low-down on a career exploration panel that took place on November 3rd in Sackler 114, sponsored by the GSC, TBBC, and the Sackler Dean’s office. Like every great event at Tufts, there was plenty of cheese, crackers, and booze to go around. Aaron Bernstein (CMP) took the stage as emcee and introduced the eight panelists and their intended career paths, which ranged from teaching to healthcare consulting.

I’ve made you all a little cheat sheet that summarizes the main takeaway for each career path and some of the great resources provided by the panelist that can help you learn more about and prepare for the job. Hopefully one or more of these professions spark your interest and inspire you to join a club, participate in an event, or simply give you something new to think about!

  1. Joslyn Mills-Bonal (CMP), teaching

Inspired by her great experience at a small liberal arts college, Joz participated in the panel as an advocate for a teaching-heavy career at a community college, liberal arts college, or university.  

Teaching experience, which might seem hard to find at Sackler, is critical for preparing you for this job. Take advantage of student seminars and treat them as an opportunity to practice teaching. You can work on your curriculum design skills by getting involved in behind the scenes efforts for the various teaching opportunities you participate in. For example, if you get involved with Biobugs you can also take part in designing the labs.

It’s important to think about what kind of institute you want to work for- a liberal arts college? A state university? A research I institute? These decisions will inform the steps you take during and after graduate school as you work towards your career as a teaching professor. For example, a postdoc is usually required for a job at a liberal arts school and above, whereas community college professors don’t need a PhD. Also keep in mind that if you don’t want to continue to do research, your publication list isn’t so important. If you do want to continue to do research, however, you need to keep in mind that prolific publishing is paramount.

Opportunities/resources of interest:  

If you’re interested in any of the above opportunities or simply want to learn more about this track, feel free to contact Joz!

  1. Laura Stransky (CMP), academic/industry science

In academia we aim to better understand some disease or mechanism, whereas those in industry work to make some therapeutic or drug that can be marketed and sold. For both jobs, however, Laura loves the fact that you get the luxury of thinking for a living!

As a graduate student at Tufts, you’re already actively in training for a career as a scientist! To make the most of your time in graduate school, go to seminars as often as possible and learn from how other people present. Remember that for many of the visiting speakers there is a lunch you can attend with the speaker at which you can network and learn about their career path. Take any and all opportunities to write! There are plenty of grants travel awards, abstracts, and conferences that give you the chance to practice writing. By taking mentoring opportunities—volunteering to work with rotating students, for example—you can develop the management skills that are critical to being a good scientist, regardless of whether you’re in industry or academia.

After graduate school you must become a postdoc if you intend to get a job in academia. You need to demonstrate your ability to accrue funding and publish high impact papers. If you’re leaning more towards becoming a scientist in industry, a postdoc isn’t absolutely essential but can certainly get you started a little higher on the ladder. Furthermore, a postdoc before industry can help you expand your skills, fill in any gaps that you may have, and perhaps give you the opportunity to get involved in more translational research and develop project management skills.

  1. Kayla Gross (CMDB), science communication

This field encompasses more than just one kind of job—you can be a medical writer, a publisher, a communicating officer at a brand, or even a journalist. While at Tufts, find ways to improve and practice your writing and communication skills! Look for as much feedback as you can on your manuscripts, abstracts, posters, presentations and even committee reports to help you sharpen your skills and hone in on what needs to be improved. You need to practice adaptability to different scientific fields, since as a writer you are unlikely to be limited to just one topic. Furthermore, you need to be able to speak to those who aren’t well versed in the field you are writing about.

For a job in science writing, there is no hard and fast rule on whether you need to postdoc or not. The only track in which working as a postdoc is encouraged is in being an editor. If journalism is your goal, keep in mind that making the shift from grad school to journalism can be tricky—you may have to do some freelance writing for a while to build up your portfolio and break into the field.

Opportunities/resources of interest:  

  • Join the INSIGHT newsletter/blog! You can participate as much or as little as your time permits, and it’s a great opportunity to practice your writing and communication skills. Contact Kayla to join!
  • Tufts also has a collaboration with Emerson College in which you can work with an undergraduate communications student whose project is to assemble a science-centric media piece in which your research is explained to the general public. This is a great way for you to practice making the science that we think so deeply about a digestible subject for the general public!
  1. Andrew Hooper (Neuro), science policy

A job in science policy often involves advising policy makers on important scientific matters. This is a great way to have impact on our government and every day lives by helping educate people, especially politicians, who often have very minimal science knowledge. Because part of the job also often involves putting budgets together, it’s important for you to have some financial savvy. Finally, communication skills are essential, as you’ll be translating complicated scientific concepts to people completely untrained in the field.

There are many organizations that offer policy fellowships that can support you while you work in D.C. and learn the ropes, most of which require a postdoc. Applications are usually due in January and start dates are in the fall.

Andrew suggested you contact him if you’re interested in science policy!  

  1. Matthew Kelley (Neuro), data science

Data science merges statistics, math, and programming to help get insight from large databases, generate correlations, and make predictive models.

Hard skills you need for a job in data science include statistics, programming—many things you are already doing regularly as a PhD student. It’s important to learn how to code, which you can do on your own! While you’re at Tufts, try to integrate data science in your PhD project to practice applying your skills.

Opportunities/resources of interest:  

  • The Insight Science Data Fellowship, designed to bridge the gap between a non-computational graduate degree and a career in health data science (http://insighthealthdata.com/). In this program, you’re funded for 7 weeks to learn from industry leaders and even interview with some of the top companies in the industry!
  • Check out the newly formed Data Science Club—there have only been two meetings so far so get in early! The club plans on bringing in speakers and learning applicable skills together.
  • MIT edX has a course on analytics: https://www.edx.org/course/analytics-edge-mitx-15-071x-2
  1. Jaclyn Dunphy (Neuro), entrepreneurship

A job as an entrepreneur is exciting because it involves brainstorming and sharing ideas with other people to start something completely novel. A job at a start-up company might seem high risk, but it offers the opportunity to make a big impact, as teams are usually small. If you’re interested in being a “big piece of a small system,” this field might be for you!

Firstly, to be more proactive, reach out to others—contact experts who can assess your idea and help you decide how feasible it is. Secondly, demonstrate leadership skills! Take the lead with rotation students and get involved in student-run groups where you can take some charge! Thirdly, practice your interpersonal and networking skills. You must practice the formula to successful networking: reaching out to your person of interest the day after meeting them, be it via e-mail or LinkedIn, and setting up a time and day for a coffee meeting where you can learn more about their job and solidify your professional relationship. To get started as an entrepreneur, the best thing you can do is… be an entrepreneur! Think of an idea and start a company!

Opportunities/resources of interest:  

  • Cross register for classes in the entrepreneurial management program at the Medford campus
  • Engage in IDEAS competitions
  • Participate in Mass Challenge!
  • Venture Café: A networking event that happens every Thursday evening at the Cambridge Innovations Center (1 Broadway, Kendall Square, Cambridge MA) where you can have a (free!) drink and socialize with other entrepreneurial-minded people. This can be a great opportunity to find collaborators or just bounce your ideas off other people in a social and friendly environment.
  1. Michaela Tolman (Neuro), healthcare consulting

Michaela aptly nicknamed healthcare consulting “rent-a-brain”—a perfect summary for a job in which you are hired to consult non-experts in a healthcare related venture. Many of us are in biomedical research because we want to help people, but as we all know, research can be slow and it might take years or even decades before a discovery you make in lab actually benefits someone in the clinic. As a consultant you are involved in helping bring people the best healthcare much more rapidly.

It’s extremely important to develop interpersonal and networking skills for a successful career in consulting! The job involves a lot of interactions with non-scientists and you need to be able to fit in and make them feel comfortable. It’s also important that you have business acumen and learn the jargon of the business world. Do you know what people are talking about when they say percent market share, market size, or competitive landscape?

To go on consulting interviews, you have to be able to say that you can graduate within a year. Postdocs are not recommended as consulting firms are typically looking for someone fresh out of graduate school. It’s also critical that you know how to do a case interview, which typically the process one goes through before getting a consulting job.

Opportunities/resources of interest:  

  • Join the case study groups, which take place every Monday!
  • Participate in TUNECC- this is a highly attended case-competition event at which you can show off your consulting skills and get the attention of potential hirers!
  • Come to Biotech Buzz and Tufts Advisory Partners (TAP)!
  • Michaela also had some book recommendations, including Case Interviewing Secrets and Case In Point.
  • A website that might interest you is Seeking Alpha.
  • The “Mini MBA” program at Harvard can be great for your resume
  • Just like for any other career path, network, network, network!
  1. Christina McGuire (Biochem), venture capital

Though there are venture capital firms that solely exist to provide funding for start up companies that already have a formulated product or idea, Christina’s goal is to find a job in a venture capital company that creates ideas in-house. To get that kind of position, you need to have a deep understanding of science and you definitely need good analytical skills. Continue to practice reading primary literature to develop these skills and also keep in mind the importance of acquiring business acumen. Often times, to get a job at a VC firm, you need to get involved in business or consulting first. Demonstrate your entrepreneurial abilities by getting involved in successful projects and familiarizing yourself with the business world, much like when you are preparing for a career in entrepreneurship and consulting!

Opportunities/resources of interest:  

  • Tufts Biomedical Business Club (TBBC) and Biotech Buzz.
  • Christina’s book recommendations: Venture Deals by Brad Feld and Jason Mendelson.
  • Subscribe to: Fierce Biotech and XConomy

Overall, the event was a great success and attendees walked away with a wealth of knowledge and tips for how to better prepare for a slough of career options. A major recurring theme throughout the night was the importance of networking, so as intimidating as it may seem, the next time you hear about a networking event, grab a friend and go! You never know if the next person you meet will help open the door to your dream career.

GSC Committee & Club Updates: October 2016

Tufts Biomedical Queer Alliance (TBQA)

by Laura DarniederNRSC

First General Meeting!
Join LGBTQIA colleagues from the Medical, Dental, and Sackler schools on Wednesday 12/12 at noon in Sackler 114W for free dumplings and to learn about this year’s upcoming events!

Tufts Biomedical Business Club (TBBC)

from Jaclyn DunphyNRSC

The Tufts Biomedical Business Club (TBBC) is a student run organization whose mission is to cultivate business leaders in the health and life sciences. TBBC is a growing community of graduate, medical, dental and nutrition students, postdocs, physicians, scientists and alumni. It provides members with opportunities to learn about consulting, business development, entrepreneurship, intellectual property and more.  We engage our members though a number of initiatives including a seminar series, Biotech Journal Club, Consulting Case Study Group, panel discussions, Biotech BUZZ and most recently the Biomedical Data Science Club. E-mail tuftsbiotech@gmail.com for more information.

Recent Events:

TBBC Seminar Series: Seismic – W Sep 21: The founders of Scismic, a tool aimed at helping researchers to find their optimal work environment/mentor, met with students and postdocs for feedback on the company’s product and business model.

TBBC Tufts Advisory Partners – After a successful first engagement last year, TAP’s second engagement is now well under way.

Upcoming Events:

TBBC Case Study Group: Mondays – 5-7PM, Jaharis 508

Practice solving cases, gain insight and tips, and learn more about the field of consulting.

 

 

TBBC Tufts Biomedical Data Science Club: Information Session:   Tu Oct 11 — 5PM-7PM, Sackler 221

The Tufts Biomedical Data Science Club will be a resource for students wishing to learn and apply programming techniques in order to tackle big data problems in the biomedical sciences. No programming experience required! The club will host bi-monthly meetings, work on group projects, and provide opportunities to hear invited speakers and network with others interested in big data. Please email Matt Kelley at matt.kelley@tufts.edu with any questions.

TBBC Biotech Buzz with Hannah Mamuszka: F Oct 21 — 9AM-10AM, M&V Lobby (Stearns 108)

Picked by Future of Biopharma as one of 5 women to watch in Boston, Hannah Mamuszka is the founder and CEO of Alva10- a company specializing in precision medicine. Hannah will be joining us for an informal conversation about the latest news in biotech, her career, and Alva10.

TBBC, GSC, and the Sackler Dean’s Office Career Exploration Panel: Th Nov 3 — 5PM, Sackler 114

A panel of senior graduate students will provide insight about steps that newer students can take to prepare themselves for a variety of career paths, including: academic/industry science, teaching, entrepreneurship, science communication, policy, data science, venture capital, and consulting.

ICYMI: Mentoring Circles Kickoff

As part of my resolution to better understand my career goals and options by attending more seminars at Tufts and then sharing my experiences with you, I decided to join the Tufts Mentoring Circle Program. Here’s a brief breakdown of the program’s kickoff event, which was held on October 6th in Sackler 114.

For those of you who are unfamiliar with the program, the mentoring circles, open to all graduate students and postdocs at Tufts, are meant to provide a social and educational experience for mentors and mentees alike, bringing together people who, based on a previously submitted survey, have similar career goals and interests. At this first event, the circles, which have an average of five or six people per group, were brought together to meet one another and discuss objectives for the year. Since on my survey I indicated a strong interest in industry, my group consists of postdocs with the same inclination and a mentor who currently works as a scientist at a prominent pharmaceutical company in Cambridge. My experience will be unique to my personal goals, as those who stated an interest in academia are grouped with other academia-bound grad students and postdocs, similarly to how those who are working towards an alternative non-academic career, like science writing, are also assigned to one another for the duration of the program.   

After we introduced ourselves within our groups over pizza and salad, the organizers of the program gave a short presentation on tips and suggestions for how to have a successful circle. The importance of preparing for and attending every meeting was heavily stressed. We were also encouraged to mix up the format our meetings—instead of always just going to a coffee shop and talking, we can go to events together like symposiums, seminars, or even networking events. As someone who finds networking to be an intimidating and nerve-wracking experience, the prospect of having someone come along and act as a safety net seems fantastic and will make me more likely to attend.

After the presentation, groups were left to themselves to chat, set goals, and eat more pizza. In my group, every person had the opportunity to talk about what their dream job might entail—whereas some of the members had pretty specific career ideas, others, including myself, could only speak in broad strokes about factors like work-life balance, travel, and flexibility. The meeting was casual and fun, and it was actually a relief to hear some postdocs, even a few years out of graduate school, have undeveloped ideas about their careers and are still figuring out where they want to end up. Together, we decided on topics that we would like to discuss and goals that we would like to achieve throughout the year and we signed a “Mentoring Circle Contract” that stated the following: “We understand that each of us is responsible for maintaining the confidentiality of our shared communications, meeting regularly at the times we have agreed upon, and actively participating in circle discussions”.  Though this was only our first meeting, I can tell we all have a lot to learn from one another and I am excited for the new professional and friendly circle I am now a part of! It’s like joining a club where the main project is you and your career.

Definitely keep an eye out for the program’s announcement next year, and also keep in mind that American Women in Science (AWIS) is another organization through which some of you can join a similar circle.