Category Archives: articles

articles, December 2016, Techniques

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.
articles, December 2016

Precision Medicine: Too Big to Fail?

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In January 2015, President Obama announced the launch of the “Precision Medicine Initiative”, proclaiming it to usher in “a new era of medicine that makes sure new jobs and new industries and new lifesaving treatments for diseases are created right here in the United States.” In addition, he remarked that the promise of this initiative laid in “delivering the right treatments, at the right time, every time to the right person”. This initiative, with bipartisan support in the Congress, provided a total of $215 million investment in 2016 for the NIH, along with the FDA and the Office of the National Coordinator for Health Information Technology (ONC), with a large portion of the money ($70 million) awarded to NCI to “scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment”. The initiative doesn’t stop at the genome level, as Dr. Francis Collins, Director of the NIH, pointed out in an interview with PBS News Hour, and is meant to provide information about environmental exposures, lifestyle choices and habits and pretty much everything that can affect one’s health. Given the mass of information that will be generated (the initiative aims to enlist 1 million volunteers for its cohort), it is no surprise that patient privacy issues, as well as database infrastructure, are major concerns in this mammoth undertaking.

In addition to this initiative, the US government also launched its “Cancer Moonshot Program” a year later in January 2016. This program, under the leadership of Vice President Joe Biden, and with the help of an expert panel, the “Cancer Moonshot Task Force”, aims to “make more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage.” Since cancer is widely accepted to be a genetic disease, it seems fitting to serve as the poster child for an initiative that aims to cure and prevent diseases based on tailoring therapy for an individual using personal genetic information.

Tied to these two initiatives is also the latest approach to clinical trials at the NCI, commonly termed as “basket trials”. Based on findings from exceptional case reports where patients treated with drugs not commonly used for that type of cancer, the NCI was encouraged to try out drugs traditionally reserved for particular types of cancer for the ones that they weren’t developed for; thus, the Molecular Analysis for Therapy Choice (MATCH) and the Molecular Profiling-Based Assignment of Cancer Therapy (MPACT) trials were incorporated into the Precision Medicine initiative.  The NCI-MATCH trial aims to sequence tumor biopsy specimens from ~6,000 patients to identify mutations that will respond to targeted drugs selected for the trial; these drugs are already approved by the FDA for certain cancer types or are being tested in other clinical trials. On the other hand, the MPACT trial will compare whether patients with solid tumors fare better with targeted therapy vs non-targeted therapy.

The NCI-MATCH trial explained. Source: National Cancer Institute website.

Despite the initial fanfare, the recently released NCI-MATCH major interim analysis report does not paint a pretty picture for the trial’s outcome. While the enrollment was higher than expected (795 people registered in first 3 months compared to the projected 50 patients/month) and the labs were able to sequence most of the tumors (87%), it was also found that “most of the actual mutation prevalence rates were much lower than expected based on estimates from The Cancer Genome Atlas and other sources”. In fact, the overall expected mutation match rate was adjusted to 23% for the 24 treatment arms in the study as it continues.

While no endpoint has yet been reached to draw conclusive remarks about this trial, data available from other clinical trials that have taken a similar approach do not seem favorable. In the SHIVA trial, a randomized phase II trial carried out in France where 99 patients were treated based on identified mutation(s) compared to 96 patients treated with drugs of their physicians’ choice, median progression-free survival was 2.3 and 2 months, respectively. Current clinical data on patients with relapsed cancers, a major focus of the MATCH trial, do not seem favorable either. As Dr. Vinay Prasad, a haematologist-oncologist at Knight Cancer Institute, points out, only 30% of such patients respond to drugs based on biological markers and the median progression-free survival is 5.7 months. Based on this response rate, he estimated only 1.5% of patients with relapsed and refractory solid tumors to benefit from the precision medicine approach.

In a review of current clinical trials and past trials that have used the targeted therapy approach, Tannock & Hickman (NEJM, 2016) warn about the limitations of such an approach – heterogeneity and clonal evolution of cancer cells when challenged with targeted therapy, the inconsistency between expected and clinically achievable levels of inhibition of candidate molecules and of course, the efficacy of such therapies compared to currently available, standard but effective therapies such as aromatase inhibitors for breast cancer. While one can argue that heterogeneity in tumors can be countered with combination targeted therapy, the authors point out that “combinations of molecular targeted agents that target different pathways have often resulted in dose reduction because of toxic effects… in a review of 95 doublet combinations in 144 trials, approximately 50% of the combinations could use the full doses that were recommended for use as single agents, whereas other doublets required substantial dose reductions.” Even if it is possible that intratumoral heterogeneity can be countered with combination targeted therapy, a much-overlooked point in this initiative is the cost of such treatment strategy, considering the exorbitant costs of targeted cancer therapy. There already exists a disparity among cancer patients from a socio-economic standpoint and this initiative does little to address how to bridge such a gap. Questions such as how many drugs will a patient have to take, especially in cases of tumors that are highly heterogeneous, such as glioblastoma multiforme and how that would affect the living standard of a patient need to be considered before heralding a victory for the precision oncology approach even if the MATCH trial outcomes are favorable.

In another recent study, Dr. Victor Velculescu and his team from Johns Hopkins showed that sequencing only tumor genetic data can lead to false positives. After analyzing 815 cancer patients’ tumor sequencing data and comparing that data to the one from the patients’ healthy tissue, they found that 65% of genetic changes identified with tumor-only  sequencing data were unrelated to the cancer and therefore, “false positives”. The team also found that 33% of mutations, which are targets of currently available drugs, were also false positives when the patient’s germline genome was compared to the tumor genome; this affected 48% of the patients in their cohort.

This is not the first study of its kind to warn against false positives when trying to identify disease-causing mutations. Findings from the Exome Aggregation Consortium (ExAC), the largest catalogue of genetic variation in the protein-coding sequence of the human genome,  show that out of the 54 (on average) “pathogenic” mutations present in an individual’s genome, 41 of them “occur so frequently in the human population that they aren’t in fact likely to cause severe disease”. This is in direct contrast with studies that seem to enforce the idea that there are many more “oncogenes” to be found that can serve as novel drug targets.

The paradigm behind the MATCH trial, and in general the Precision Medicine initiative, seems to be blind to an obvious aspect of biology – context matters, and more so, in case of mutations that are deemed to be “carcinogenic”. As outlined in a recent paper by Zhu et al (Cell, 2016) and the famous “bad luck” paper by Tomasetti and Vogelstein,  it appears that the stem cells and their differential regenerative properties in different tissue types are responsible for the differential rates of carcinogenesis in various tissue types, a finding that again, buttresses the idea that tissue specificity matters. In fact, Iorio et al (Cell, 2016) was able to show just that in the context of pharmacogenomic interactions of currently available cancer drugs with data available from patient samples in the TCGA and other databases. Using a big data and machine learning approach, the authors developed a logic-based model that would predict the efficacy of any drug that is either approved or undergoing clinical trials against the mutation it is intended for in different cancer types ,which is essentially the basis of the MATCH trial. Surprisingly, it appeared that tissue specificity determined the pharmacological agents’ effects on the intended molecular targets; more specifically, only one drug interaction (out of 265 drugs tested) was found to be significant in multiple cancer types, which may sober up the expectations from the MATCH trial outcome. Therefore, using a blanket approach to target mutations in various tissue types without consideration to their environments can seem futile in the light of such findings.

The evidence from all these basic science and clinical studies raise the question of whether precision medicine is doomed to fail. While the gene-centric view of disease etiology have deepened over the years since the completion of the Human Genome Project, does this evidence point to the necessity of another paradigm in our understanding of cancer and other complex diseases, whose cures have been presumed to lie in genetic aberrations and molecular targets? An even more concerning question, relevant in this era of big data, is whether we actually understand what the data is telling us, as the prominent cancer researcher, Dr. Robert Weinberg, admits that “while data mining, as it’s now called, occassionally flags one or another highly interesting gene or protein, the use of entire data sets to rationalize how and why a cancer cell behaves as it does is still far beyond our reach”. A strong critic of the initiative, Dr. Michael Joyner from Mayo Clinic, opines that while “hundreds of genetic risk variants with small effects have been identified…But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases” and that “when higher-risk genetic variants are found, their predictive power is frequently dependent on environment, culture and behavior”.

The success of Precision Medicine Initiative, and in particular, the precision oncology approach, ultimately rests on whether it can stem and curb deaths resulting from cancer and other complex diseases, based on molecular targeted therapy. Unfortunately, it appears that large scale public health initiatives have done more to that end (e.g. – tobacco control has largely cut down rates of lung cancer incidence, diet and exercise can cut down the risk of converting pre-diabetes to diabetes by nearly two-thirds), compared to what targeted therapy have achieved. However, it seems that such public health success was overlooked by the Cancer Moonshot panel as in February 2016, right after the program was announced, public health researchers across the country had to urge the Vice President to make prevention a bigger focus in controlling cancer incidence in the population, rather than just trying to find a cure. This approach should have been incorporated into a billion-dollar initiative by default, one would think, but this didn’t seem to be the case and one must wonder why.

In order for this huge, publicly-funded initiative to achieve more than just lukewarm outcomes and to actually become a breakthrough it is promised to be, the Precision Medicine initiative needs to break free of the gene-centered tunnel vision and incorporate all factors that affect an individual’s health, such as lifestyle choices and environmental exposures, as Dr. Collins boasted it to be. While this initiative is only at its infantile stage, changes based on clinical trial and basic science evidence should be made early enough so that favorable outcomes can be achieved and does not require the government to stage another public bailout as it did for the failing banks and wall street corporations back in 2008 when they were deemed to be “too big to fail”.

articles, Events for Students, GSC, Mentoring & Outreach, November 2016

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 Panel: December 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.

articles, Events for Students, November 2016

Dr. Tyler Jacks to deliver Charlton lecture, following poster competition

The 41st annual Charlton lecture will be held on Wednesday, November 30, 4-5.30 pm, in the Sackler Auditorium. The lectureship, established in 1975 in honor of Mr. Earle P. Charlton, has since evolved to include a poster competition that serves as a platform to recognize outstanding research work performed by graduate and professional students on the medical school campus. This year, the poster competition will be held on Tuesday, November 29 and Wednesday, November 30 in Sackler 114. Details regarding participation, eligibility and review criteria can be found here – http://sackler.tufts.edu/Student-Life/Student-Awards/Charlton-Poster-Award. The deadline for submitting abstracts for the competition is Thursday, Nov. 9, 5 pm. Please submit your abstracts electronically to Rachael Bailey at Rachael.Bailey@tufts.edu.

The keynote lecture will be delivered by Dr. Tyler Jacks, Professor of Biology at Massachusetts Institute of Technology (MIT) and Director of the David H. Koch Institute for Integrative Cancer Research. His talk is titled “Engineering the Cancer Genome”. 

Mr. Earle P. Charlton was a renowned entrepreneur and a social benefactor, as exemplified by his legacy, the Charlton Trust. Mr. Charlton established a chain of stores throughout Massachusetts back in 1890, before merging with the Woolworth company and expanding to the west and Canada. The Woolworth company would later go on to acquire several brands throughout the twentieth century. However, due to increased competition in the retail sector, the company chose to focus on a select brands and is today represented by the Foot Locker stores. Mr. Charlton passed away in 1930, and is commemorated by the Charlton Memorial Hospital in Fall River, MA, a town which benefitted greatly from his entrepreneurship and generosity. (Source – https://en.wikipedia.org/wiki/E._P._Charlton_%26_Company)

About the Speaker

Dr. Tyler Jacks is the Professor of Biology at MIT, the Director of the David H. Koch Institute for Integrative Cancer Research and a Howard Hughes Medical Investigator. He has served on public and private advisory panels on cancer research and also sits on the board of directors for Aveo Oncology and Thermo Fisher, Inc. His expertise in the field is of no surprise given his pedigree – Dr. Jacks completed his PhD under the guidance of Nobel Laureate Dr. Harold Varmus at University of California, San Francisco, and went on to do his postdoctoral work with Dr. Robert Weinberg at the Whitehead Institute, both of whom were pioneers of the field. His work has earned him prestigious awards including the Paul Marks Prize for Cancer Research and other accolades.

Dr. Jacks’ research focuses on the “genetic events contributing to the development of cancer” using mouse models that have been engineered to carry clinically relevant mutations. His lab works on a number of different cancers that range from lung, pancreatic and ovarian cancers to peripheral nervous system tumors, astrocytoma and retinoblastoma. A major focus of his current research is to develop more powerful and accurate mouse models of cancer using cutting edge genetic technology.

More detailed information regarding his work can be found on his lab website.

articles, November 2016, Techniques

Top Techniques: NMR

What is NMR?
Nuclear magnetic resonance spectroscopy, or NMR spectroscopy, is a powerful technique that uses the magnetic properties of atomic nuclei to elucidate the chemical and physical properties of the atom or its molecule. The nuclei of certain atoms, such as 1H or 13C, align themselves with magnetic fields in nuclear energy levels known as ‘spin states.’ When molecules are placed in an external magnetic field and irradiated with radiofrequency (RF) waves, certain atomic nuclei present in the sample absorb energy. These RF waves flip nuclei from one spin state to another. If the RF is turned off, the nuclei relax, releasing energy in the form of RF waves, which are measured as the decay in signal intensity over the course of a few seconds. The time domain of these signals is converted to the frequency domain to produce a spectrum, what we normally think of as the output of an NMR experiment.

But what can you actually do with NMR? Traditionally, the technique has been used to identify molecules and determine their 3D structures. It can certainly do this; however, the actual range of applications for this technique is much wider. With metabolomics approaches, you can quantify biofluids and tumor and tissue extracts. Binding events, even very weak ones, between two proteins or between protein and DNA can be detected. You can also determine the stoichiometry of these binding events. Trying to compare a wild-type protein to its mutant variant? Characterizing the active site of your protein of interest? NMR can handle both of these tasks, and measure dynamics of the protein in its active conformation as well. To that end, NMR can also be used in live-animal imaging. If you’ve ever had an MRI, you may know that the technique is actually based on the science of NMR!

Figure 1. 1H-15N 2D spectrum of BPV-1 E2 DBD (310-410). Resonances of the DNA-bound protein (red) show chemical shift differences relative to the DNA-free sample (black) (taken from Veeraraghavan et al. Biochemistry (1999) 38: 16115-16124).
Figure 1. 1H-15N 2D spectrum of BPV-1 E2 DBD (310-410). Resonances of the DNA-bound protein (red) show chemical shift differences relative to the DNA-free sample (black) (taken from Veeraraghavan et al. Biochemistry (1999) 38: 16115-16124).

What facilities does Tufts have for NMR spectroscopy?
The Tufts NMR Center currently has 3 NMR spectrometers, all located in an environmentally controlled laboratory on the 6th floor of M&V.

The Bruker DRX-600 spectrometer used for structure determination of large protein domains and small proteins, as well as metabolomics experiments. It offers the highest resolution and sensitivity of the three instruments.

The Bruker AMX-500 spectrometer is good for examining peptides and small protein domains.

The Bruker DPX-300 spectrometer is useful if you need to check the identify or purity of products of organic synthesis. The system is set up to look at nonstandard nuclei, such as 11B.

The NMR Center is also in the process of upgrading the Bruker DRX-600 by replacing the console electronics. With this upgrade, features such as non-uniform sampling and cryogenic cooling, which can double the sensitivity of 2D and 3D experiments. Other upgrades to the hardware will increase the reliability, ease of use, and speed of data collection for this system. Users will be able to study the structure and dynamics of proteins and protein complexes with high molecular weights and limited solubility, which is limited by the current sensitivity of the instrument.

Information about the spectrometers available in the NMR Center can be found at the following website: http://medicine.tufts.edu/Faculty-and-Research/Core-Research-Facilities/Tufts-NMR-Center. With questions or for help planning an NMR experiment, please email Dr. Jim Baleja at Jim.Baleja@tufts.edu.

If you are interested in reading more about NMR spectroscopy, Bothwell and Griffin wrote a straightforward but in-depth article (Biological Reviews (2011) 86: 493-510).

articles, Community, November 2016

On Unity Found in Biomedical Research

The Diversity and Inclusion page of the Tufts website includes colorful bar graphs on the university population. Sackler is 62% female and over 15 different countries are represented. Much beauty can be found in exploring our diversity, but much can be also gained from learning what unifies. Here at Sackler, many of us study this unity.

My research focuses on the disease of epilepsy, but I find the work rewarding and worthwhile because of the potential to find common mechanisms on how human brains work. Many unifying discoveries on the human system have come from study of disease. Take the textbook case of Patient HM, who had both sides of his temporal lobe surgically reduced to cure his epilepsy. Through studying him during learning tasks, Dr. Brenda Milner demonstrated in the 1950s the existence of episodic and procedural memory. In neuroscience today, cognition and consciousness are two remaining Holy-Grails, and both are affected in epilepsy. Epileptic individuals often suffer from cognitive disorders. In studying consciousness, investigators such as Dr. Hal Blumenfeld at Yale have used the transient impairments of consciousness observed in epilepsy to discover a “consciousness system” network in the functioning brain. The study of disease unveils the nature of the working machine.

Many different diseases are studied at Sackler, but looking at the big picture, what many of us are engaged upon is a search for unifying truths about the human condition. We are creating knowledge of what unifies. If you discover one truth, one singular truth of how the human body works, it is a truth that applies to all, to every group represented on the Tufts Diversity and Inclusion page. This is an empowering thought.

articles, Community, Events for Students, GSC, Mentoring & Outreach, November 2016

Take Part!

Remember student council elections in high school? Typically the most popular student running would win, but everyone was full of enthusiasm and excitement to attain those coveted positions! Fast-forward a decade or so to filling positions in organizations like the student council during graduate school and the picture looks dramatically different. We each take a turn, but we tend to do so grudgingly. High school was grueling, don’t get me wrong, but as the years progress the demands on our time change, the expectations are different, and the student body is less diverse (no more Poli Sci majors to eagerly take on the class president position).

Organizations that support fellow trainees and coworkers are typically run by volunteers. Each year we need people with a fresh perspective to step up and help with maintaining organizations such as the Graduate Student Council, the Sackler InSight, the Post-Doc Association, and, up here in Maine, the Research Fellows Association. There are so many important career and social events that just would not happen if these organizations were to disappear, not to mention how much smaller our voice within the school would be.

Teamwork

If you find yourself holding back from taking part in one of these community serving groups because you simply don’t have time between experiments, think of participation as a convenient way to get some career development in. Those of us who have been shoehorned into leadership positions can tell you firsthand how much rigorous practice we get in using the “soft skills”. In the business vernacular these include but are not limited to social and emotional intelligence, ability to develop people, delegation, structure and tactile development (how you get stuff done and how you tweak things to make sure it keep s getting done), style flexibility, and focus1.

Experience on a leadership team will create a tangible CV bullet that is particularly important for anyone interested in going into industry, but such experience will also be very helpful for people staying in academia (think committee and ancillary duties). It’s all in how you frame your skills to your audience.

Any of the students currently serving on committees or volunteering in other capacities will be more than happy to share their experiences, what their responsibilities and time commitments have been, contacts they have made, and what they have gotten out of their service in terms of personal and professional development.

  1. For a more in depth explanation on these soft skills, see SciPhD competencies and SCIPHD.com
articles, Community, Events for Students, GSC career events, November 2016

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.

articles, Community, Events for Students, October 2016

2016 Voter Registration Deadlines Are Approaching

The 2016 General Election will be held Tuesday, November 8, but in order to participate, you must be registered to vote by the registration deadline.

The voter registration deadlines vary by state, so it is important to check these dates and also to make sure you’re registered. A free, online service that can help is TurboVote, a project by the non-partisan nonprofit Democracy Works that aims to make voting easier. TurboVote will direct you to the appropriate Secretary of State’s website to check your registration or register to vote. Many states, including Massachusetts, offer online voter registration if you are a legal resident and have a state driver’s license or identification card. You can also sign up to have TurboVote send you election day reminders by text or e-mail.

In Massachusetts, the voter registration deadline for this year’s election is Wednesday, October 19. Election-related information is available on the website of the Massachusetts Secretary of State (http://www.sec.state.ma.us/ele/eleidx.htm). Many resources are available, including to check your registration status, find your polling location, request an absentee ballot, find information on candidates and ballot questions, and register to vote if you are eligible.

Disclosure: Neither I nor the InSight were asked to publicize TurboVote and Democracy Now, and we are not receiving compensation for doing so.

articles, Events for Students, October 2016

Harold F. Dvorak, M.D., invited to deliver 11th Annual Jeffrey Isner Lecture

The 11th Annual Isner Lecture is scheduled to be held on Wednesday, November 2, 2016, 4 pm at Behrakis Auditorium in the first floor of the Jaharis building. In keeping with the tradition of inviting speakers who have made significant contributions to the field of angiogenesis-related research, this year’s speaker will be Harold F. Dvorak, M.D., credited with the discovery of the Vascular Endothelial Growth Factor (VEGF). Dr Dvorak’s talk is titled “VPF/VEGF, Angiogenesis and Stroma Formation: The Tumor Vasculature as Therapeutic Target”.

 

About the lectureship & Dr. Jeffrey M. Isner

The Jeffrey M. Isner, M.D. Endowed Memorial Lectureship was established in 2007, in honor of Dr. Jeffrey Isner, a graduate, and later, a faculty member, of the Tufts Medical School. This lectureship is meant to provide an opportunity to bring the Tufts medical and biomedical communities together to “ to reflect upon and consider the pioneering work of Dr Jeffrey Isner.” The lectureship also invites a keynote speaker, chosen from the internationally recognized pioneers in clinical and/or basic science research communities focusing on angiogenesis-related research, vascular biology and cardiovascular medicine.

Dr. Jeffrey M. Isner, Source - Tufts Medical School website
Dr. Jeffrey M. Isner, Source – Tufts Medical School website

Dr. Isner was a pioneer himself, as evidenced by his profession as an interventional cardiologist, a nascent medical field at that time. He is also known for his novel therapeutic approaches, such as combining gene therapy and angioplasty to treat blocked blood vessels in patients. While treating a patient in 1994 for a blocked vessel in the leg, Dr. Isner and his team coated the angioplasty balloon with genes to express VEGF in an attempt to observe whether the VEGF protein would be able to promote the growth of new blood vessels that would bypass the blocked artery. While clinical gene therapy applications were still years away, his attempts and results were deemed promising by his peers. Dr. Isner was also actively involved in bringing his approach to the market – he was a founder and a major stockholder in the company Vascular Genetics, based in North Carolina. Not surprisingly, his involvement in the industry resulted in some critics to suggest that this could affect his medical judgement, suggestions that were rejected by Dr. isner. In 2000, the FDA suspended research carried out by the company and St. Elizabeth’s on the grounds of possible improper reporting on death of patients enrolled in the trial. However, in Spring of 2011, his research was allowed to resume and he was additionally awarded a $10 million dollar grant. (Nagourney 2001)

 

Dr. Isner, who passed away at the age of 53 from a cardiac arrest in 2001, is survived by his wife, Linda Hajjar, and his three children – Joshua, Jessica and Matthew. His motivation to bring novel therapies for cardiovascular diseases from the lab to the clinic stemmed from his will to make a difference, as he said in an interview in 1998 – “… the thing that really motivated me more than anything else is a sense that I don’t want to feel that I was just kind of passing through during this lifetime. I do not want to be just one more person that came and left. I always wanted to do something that could make a little difference.” (Ferguson 2001).

 

Fun fact – Dr. Isner had a walk-on role in “Seinfeld”, thanks to his friendship with Larry David, the show’s co-director, co-producer and a chief writer.

 

About the Speaker

Dr. Harold F. Dvorak. Source - www.bidmc.org
Dr. Harold F. Dvorak. Source – www.bidmc.org

This year the Isner Lectureship steering committee has invited Dr. Harold F. Dvorak, MD, Professor of Pathology, Beth Israel Deaconess Medical Center,  to deliver the keynote lecture, a choice that is befitting to honor Dr. Isner’s memory given that Dr Dvorak is internationally recognized for his discovery of VPF in 1983, later known as VEGF, and his contributions on understanding tumor vasculature. His work on the role of VEGF secreted by tumors led us to the understanding of tumors as wounds that cannot heal, but are able to sustain themselves by promoting growth of blood vessels (Ribatti 2007). This discovery opened up a whole new facet of tumor biology and a host of potential new avenues for cancer therapeutics. To this date, Dr. Dvorak and his team are working on understanding angiogenesis in tumors to the greatest detail and developing anti-angiogenic therapy for cancer treatment.

 

Sources –