Jared Smith earned his PhD in neuroscience at Penn State University College of Medicine and afterwards, pursued systems neuroscience further as a postdoctoral scholar at Penn State and Salk Institute for Biological Studies. He was a K99/R00 Award recipient, on track to start up his own academic lab, but took an unforeseen, but pleasant, detour into industry. He is currently Senior Scientist of Target Discovery at REGENXBIO, Inc., where he leads systems neuroscience projects for AAV based gene therapy in CNS diseases. Beyond his therapeutic development research work, Smith has developed a fascination with the claustrum, a brain region without a clear function identified yet. In furthering this interest, he helped co-found the Society for Claustrum Research, for which he also served as President and sits on the Board of Trustees. He has also helped host three satellite meetings at SfN and recently published an Annual Reviews of Neuroscience article on the claustrum.

Can you describe your academic and professional background? What path led you to pursue this field? 

I am a systems neuroscientist currently working at a gene therapy company developing AAV-based approaches to treating neurological diseases. I’ve had a somewhat diverse scientific career path, owing to my broadly evolving interests and tendency to jump when opportunity knocks…even if it means moving to a whole new field. 

I started out my scientific career in high school working in a genetics lab at the Penn State College of Medicine (Dr. Teresa Woods, now at Rutgers), working on breast cancer. I learned a lot about the methods of science and what “real-life” in a lab was like and decided biology was not for me. I wanted to know more about the fundamental nature of reality; I wanted to be a philosopher-scientist. So as an undergrad at Bucknell University, a small east coast liberal arts school, I majored in chemistry, but spent most of my time in physics, math, philosophy, and humanities. 

In my freshman studies seminar, “Distortions of Reality”, I was first exposed to the idea that neural processing within the brain was responsible for our entire consciousness and perceptual experience of reality. I got involved in some genuinely fun psychophysical research on visual illusions with Dr. Arthur Shapiro (now at American University) and published my first academic papers. I learned a tremendous amount about the nature of the human experience with the physical world and got my first taste of neuroscience.

After college, I luckily had a terrible time finding work in chemistry and found my way back to neuroscience. As any new college graduate with no clue about what he wants to do, I went back to hanging around college campuses, attending seminars and journal clubs about neuroscience. It was through a meeting in Penn State’s Psychology Department that I heard about an opening for a research technician job at the Penn State College of Medicine, which was great because that’s where I grew up and was once again living with my parents (as I was flat broke after graduation). I will never forget walking into the lab during my interview and the grad student was doing extracellular electrophysiology recordings from the somatosensory cortex of a rat. As I entered the lab, I heard the snap-crackle-pop of neurons for the first time, which were coming through a stereo system connected to the output of the neuronal amplifier. The grad student, my now long-time friend Dr. Shubhodeep Chakrabarti, handed me a probe and told me to touch the animal’s whiskers. As I followed his instructions, I heard the neural activity explode. Touching other parts of the animal’s body had no such effect and suddenly I had an intimate understanding of the somatotopic organization of the cortex. I was hooked.

After two years as a research tech, I stayed in the same lab to complete my doctoral work, using fluorescent dyes to trace brain circuits and subsequently characterize their role in sensory processing with electrophysiology recordings. I went on to complete a two-year postdoc studying neurovascular coupling with Dr. Patrick Drew and collaborating with Dr. Nanyin Zhang on resting state-fMRI studies. Finally, one day a friend of mine sent me a job post for a postdoctoral position at the Salk Institute in San Diego where I could learn to use AAV based approaches to manipulate neural circuits with optogenetics and DREADDs to see how they altered behavior. I applied on Saturday at noon and had an interview fifteen minutes later. After landing the job, I packed up my partner and my dog and drove across country to beautiful, sunny La Jolla and spent the next four years doing the best science of my life in the lab of Dr. Xin Jin and other famous systems neuroscientists like Dr. Ed Callaway and Dr. John Reynolds. Through the Reynolds lab, I got my first experience injecting AAVs into non-human primates, which would later prove critical to my next career step. Through that eleven years in academia, I had fully satisfied my yearning for philosophy, and when faced with the truth about the realities of grant funding, was shifting my interest into how I could use all the knowledge I had gained to actually impact the field of medicine.

How did you find this particular position, and what was the hiring process like?

My pathway to industry, particularly my current position at Regenxbio, was for lack of a better word, lucky. I mean that in two ways: (1) I found a job I didn't even know I wanted and (2) I stumbled on the job by totally fortuitous circumstances. 

After 2 years as a technician, 5 years of doctoral work and 6 years of being a postdoc (2 at Penn State and 4 at the Salk), I was fortunate to have over a dozen first author papers in top tier journals such as Neuron, eLife, and Journal of Neuroscience. I had also obtained a K99/R00 Pathway to Independence grant from NINDS to start my own lab in academia, as well as a host of other awards and grants. So as one would expect, I was sending out faculty applications to every open position. However, at the urging of my partner, Dr. Elizabeth Shakespeare (who has a PhD in education and was already working in biotech), I widened my search to include positions in industry to see what opportunities were out there.

It was through this search that I first heard about the Gene Therapy Program (GTP) at the University of Pennsylvania, which was built by Dr. James Wilson, one of the pioneers of the AAV gene therapy field. Until this point, I had only been aware that AAVs were used in animal studies and had no idea they had been used therapeutically in humans for almost twenty years. So, I enthusiastically applied to a position in the GTP, as I thought this was the best way to get my foot in the “translational research” door and start down a more applied research trajectory.

A week or so later, I received a phone call out of the blue from a recruiter. Quite frankly, I thought it was a scam as nobody had ever explained to me how recruiters work. After a phone conversation and filling out a questionnaire, the recruiter called me back and said he had two positions that I was a good fit for. One was the GTP position I’d already applied for and the other was with a company I’d never heard of called Regenxbio (which I subsequently learned had been started from the GTP at UPenn). Through the recruiter I got an initial interview at GTP, but I never heard from them again. With RGNX, I had a phone screen with a senior director (now my boss), then another director, then the Chief Science Officer. Finally, I successfully landed an in-person interview. 

I was thrilled from the moment I walked through the front door. It was like the Google of bio-tech. I spent the day interviewing with different PhD scientists from a wide array of disciplines and presented a job-talk on my AAV-based systems neuroscience research and toured the labs. Here was a place where I would be supported to develop AAV-based gene therapy approaches to treating diseases of the central nervous system, without the uncertainties of the grant-funding systems. Here was a place that had a pipeline of these therapies already working effectively in humans. Here was a place I could make a difference in science, in medicine and in patient’s lives. After negotiating the final contractual arrangements, I accepted the job, politely returned my K99 funds to the NIH, ended my postdoc (a bit prematurely) and moved my partner, child and dog back across the country to Maryland to start my career in industry.

Can you tell us about your current responsibilities? What is a typical day or week like in your role?

My current position is as a senior scientist in Target Discovery under the Research and Early Development division. Our Target Discovery group is organized into area specific teams (ocular disease, rare disease, etc.) and I am co-leading the CNS team. I report directly to the senior director of Target Discovery and manage a growing group of scientists and technicians in the CNS team. In addition to our in-house research, I also manage external collaborations with both business and academic partners. Additionally, I am involved in several cross-functional teams related to commercial development, business development, laboratory facilities design and expansion, hiring, and patient advocacy/outreach. My typical day ranges wildly from meetings related to these various functions, working in the lab and analyzing data, creating/giving data presentations, reading journal articles, writing scientific manuscripts, and squeezing in time for lunch with colleagues and going to the gym. I also email; lots and lots of emails. Compared to my time in academia though, I have a much healthier work/life balance, and I spend a lot more time with my family and doing activities beyond work. Lastly, prior to COVID, I was traveling quite a bit to attend academic conferences and meet with various collaborators.

What do you enjoy about your current job and work environment?

There are a great many aspects of my current job and company that I love. As a scientist, I am in an exciting new chapter of my career. While I am somewhat restricted in what I can pursue (e.g. it must pertain to AAV based gene therapy), the research is immensely interesting and challenging. I also have the benefit of working in a cutting-edge research environment with some of the smartest scientists I’ve met in my career. The diversity of their backgrounds is a well-spring of creativity and makes for fantastic interdisciplinary conversations over coffee breaks and during project meetings. This extends beyond science and I have learned so much about clinical operations, biological manufacturing, regulatory processes (e.g. FDA), and the biotech/business world as a whole. Academia had imprinted a pretty dark and bland impression of industry in my mind, and I have been pleasantly surprised that all those aspersions were completely false. 

What are some of the challenging aspects of your job? Is there anything you wish you had known about your job or industry before joining?

My job is very challenging due to the ultimate goal being practical application of a therapeutic to human patients. It’s one thing to do basic science research, it is quite another to achieve the same results with safety constraints. Also, as it turns out, mice are a terrible model for humans in a lot of ways. Even non-human primates have key differences that are also challenging. And unfortunately, cells in a dish have a whole separate array of pros and cons. However, you need each of these models to make progress. So, I find myself constantly dancing back and forth, assessing the capabilities and limitations of each method, to design the right set of studies to develop a therapeutic. It’s like a multi-dimensional biological rubix cube. Luckily, we have an extensive array of resources and expertise, both in-house and through external partnerships, to solve the puzzle.

Do you have any professional plans for the future? What are some future career paths that could open up for someone in your position, 5-10 years down the road?

Ahh the future!! My next steps as a hopefully upwardly mobile scientist are to build my current team and develop some successful research programs, along the way ideally being promoted to Principal Scientist and then Director. Even longer term, the sky's the limit. I may feel drawn back to academia at some point to start a lab, which is still an option, or go on to start my own company. In bio-tech, if you can dream it, you can make it true. The key is expanding your knowledge of how things work (e.g. the bio-tech space) and who makes things work (e.g. venture capital), but most importantly, identifying what the key problems are that need to be solved and thinking creatively about how to solve them.

What’s changing in your industry? Are there any future trends we should be aware of?

The field of AAV gene therapy is expanding rapidly!! It’s an incredible time to be in this field with new advancements in capsid engineering to make vectors that can target tissues in clever ways, promoter/enhancer design for targeting cellular subtypes, integrating other biological technologies with this delivery platform, and so many other avenues that will revolutionize medicine as we know it. The technology seems especially poised to make advancements on CNS diseases, so neuroscientists, climb aboard!

Also, I’ve observed that the field of immunology, pertaining to both infectious disease and auto-immune disorders, is a booming space with a significant need. This also intersects with gene therapy technologies both to make them more effective and tolerated, as well as using gene therapy to treat these ailments.

What activities, internships, or organizations would you recommend someone get involved with to help them break into this field?

The major professional societies for my field are the American Society for Gene and Cell Therapy (ASGCT) and its counterpart the European Society for Gene and Cell Therapy (ESGCT). Their conferences are excellent places to network and find relevant academic labs and companies. Internships are a great way to learn more about industry and see whether it is an avenue you want to go down. My company hosts a summer internship open to undergraduate and graduate students, as do many other companies. Lastly, the way into any position in industry is network, network, network!! This means talking to people at conferences, becoming a pro at LinkedIn, and following up. It typically takes 6-8 months to find your first job in industry, and typically it's through either a recruiter or through someone from your network recommending you. That said, it’s essential to keep in mind that industry positions are all about fit, you need to have the skills/background that the company is looking for, and even then, it's going to be competitive. 

Is it common for people in your field to have a scientific/academic background (i.e. have PhDs)? Can you think of any advantages or disadvantages someone with a PhD might experience while pursuing or working in your field?

It is very common to have a PhD in my field, and most people have also done post-docs (though that is not a prerequisite). There are many talented personnel with Master’s degrees as well who work their way up. But having a PhD is a big help and you learn a lot about how to manage a project and see it all the way through to a deliverable (in the case of your PhD, your journal articles and dissertation). An important aspect to consider is whether to do an academic postdoc or not, and for how long. A successful postdoc can help you start higher in industry, but you could potentially rise as high or higher by starting in industry fresh out of your PhD and working hard to rise. Hiring seems to go either way, sometimes companies are looking to hire an individual from academia who will have fresh ideas or experience with a new technology, but conversely, many companies want to hire scientists with a proven track record in industry who have shown they can be successful in the customs and operational paradigm of the private sector. As I said, the average time to find your first job in industry is 6-8 months, but it typically takes only 2-3 weeks to find your subsequent industry jobs. And there are typically many subsequent jobs; there’s a lot of mobility in industry.

One last hint for success is that your publications matter!! Your job as an academic is to publish papers or get patents, so you need those tangibles to show potential employers that you are a productive scientist. 

Do you have any final words of advice for those navigating these career questions?

Your career is just that: YOUR career. There are no right answers, only different paths. Ask for advice and talk to everyone but don’t feel compelled to follow any of the advice you're given, including mine! One important reason is that hiring landscapes are constantly in flux, so what was true even earlier this year may not hold true for you now. That being said, here are some suggestions that I think helped me:

Work with your university/institutional career development services to make a “resume”. I cannot stress enough how important it is to use a resume when applying for industry, as opposed to a CV, and your career development centers will be immensely helpful in getting yours fixed up. One- or two-pages MAX!! Do not list all your papers, have a link to your OrcidID, GoogleScholar, ResearchGate, etc. for the full list of your papers, and then highlight the two or three most relevant papers. Re-iterate the exact words from the job ad on your resume. If they are looking to hire someone who does qPCR, you better have qPCR obviously listed under one of your work experiences!! Which gets to the real point: tailor your resume for every different job you apply for. It's time consuming but effective, and as someone who’s sat on the other side of hiring, your job as the applicant is to make your resume stand out among the hundreds of resumes in the pile. Do your research on the company and the specific job, try to anticipate what they are really looking for (hint, it's explicitly written in the job ad) and make sure you write those attributes in your resume almost verbatim. The hiring manager will sit there and exclaim, “Wow, it's like this person was practically made for this job”. Final point on resumes, know when it's time to remove things from your past. I’m sure you’re proud of being a life-guard at the community pool back in high school, but if it's not relevant to the position, then it's just a distraction and may in fact be detrimental. 

Learn how to network on LinkedIn. Start by getting your account looking professional and accurate, meaning a professional looking headshot and a proof-read bio (nothing is worse than typos on your profile). Clearly state where you are at in your career and what your goal is. Connect with professional societies, companies, and people in the field you’re pursuing. Sounds obvious in this day and age, but it's essential, so don’t be shy and reach out. Ask to set up meetings to discuss their field or company, be genuinely inquisitive, be honest, be passionate, be human. Not every conversation will get you an interview. Not every interview will get you a job. But you’re building experiences and networks and one-day you’ll be standing on a mountain of connections and happily employed. 

Identify and establish relationships with recruiters through LinkedIn. They are out there and they are good at their jobs. Connect and then direct message them. Many of them work regionally, so if you know a part of the country (or world) you want to move to, seek recruiters for that area. Which brings up one great point, different industries have hubs in different places. For bio-tech, Boston, DC metro, San Francisco, and others are the major hubs. Consider relocating if you’re having trouble finding a position. Conversely, if you know where you want to be and can’t find work in your field, consider branching out with the type of position you’re looking for. Many of my friends from science have left the bench behind and become wildly successful in other positions that leverage their knowledge such as venture capital, consulting, medical science liaison, policy, regulatory bodies, non-profit foundation work, and many, many more.