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Research Roundup: Stephen Dewhurst Explores the Latest Bench-to-Bedside Projects

Monday, April 8, 2019

Transitions and Trials

Stephen Dewhurst, Ph.D., Vice Dean for Research

Almost 10 years ago, Brad Berk had the idea that the Medical Center should position itself to take a lead in the new field of cell-based therapies by constructing a manufacturing facility that could produce those cells under the highly regulated conditions that are required by the FDA. Brad’s vision was that, by doing this, we would enable UR to deliver first-in-human therapies to patients.

Fast forward, and the facility we built – the Upstate Stem Cell cGMP Facility (USCGF) – is working in coordination with Torque Therapeutics (Cambridge, MA) to produce modified T cells that are being infused into cancer patients as part of a clinical trial that started earlier this month.

As with most research partnerships, our relationship with Torque is fundamentally a relationship between people, and an expression of trust in the team led by USCGF Director Luisa Caetano-Davies. It’s worth noting that only two years ago, Luisa was a postdoctoral fellow in Chris Proschel’s lab. Her subsequent success and growth are the combined result of a lot of hard work, intelligence and – in no small measure – opportunities created by our URBEST program.

The Torque trial is a huge step for the USCGF because it represents the first time that a cell-based product produced by our facility has been administered to human subjects. But it’s also an important step for our Medical Center, when viewed in the broader context of our evolving approach to clinical trials.

Pat Ames is heading up a new Office of Clinical Research, working with Martin Zand, Steven Wormsley and many others to lead the implementation of a clinical trial management system to improve our clinical trials infrastructure. This system will streamline and automate many cumbersome clinical research processes and reduce administrative burden on our research teams, helping us conduct more clinical trials and offer more treatments to our patients and community members.

At the same time, Paul Barr in the Wilmot Cancer Institute (WCI) was just awarded a major new grant to support WCI involvement in National Cancer Institute (NCI) cooperative group clinical trials. This award establishes URMC as one of 30 lead academic sites within the NCI consortium, a designation rarely given to an institution that (currently) does not have an NCI-designated cancer center.

Perhaps most exciting of all, Mark Noble and Nimish Mohile recently received a highly encouraging score for a proposal that would (if funded, as we hope it will be!) launch a first-in-human trial of a new cancer treatment that is the result of fundamental research conducted in the Noble laboratory. Based on a new tumor-specific vulnerability, and discovery of existing drugs with the unexpected property of attacking this vulnerability, the new therapy eliminates cancer stem cells in glioblastoma (one of the most deadly human cancers).

This is exactly the kind of bench-to-bedside science that Brad envisaged ten years ago. We’ve made lots of progress, and there’s more to come. It’s an exciting time to be involved in research at the Medical Center.

Research Roundup: Dealing with Failure and an Unfunded Grant Application

Wednesday, January 9, 2019

Stephen Dewhurst, Ph.D., Vice Dean for Research

It’s something we rarely talk about: how it feels when a grant application isn’t funded. And yet, it’s by far the most common outcome for any such submission – an unavoidable consequence of paylines that are in the low teens or single digits.

The months between the submission of a grant and its review pass surprisingly quickly. And then time slows to a crawl.  The self-doubt and self-criticism become more insistent.  And hope flickers – such a fragile thing, in the end.

Recently, after submitting a grant application, I found myself logging onto the NIH website every day after the review panel had met, to see if the scores had been posted.  Eventually, they appeared.

This particular grant isn’t going to be funded.

It’s a horrible feeling.  A private hurt that’s immeasurably hard to share with colleagues, family and friends. That’s because the narrative is one of failure.

But, I’ve chosen to write about it anyway – because we’ve all been here.  Because shame thrives in secrecy and loses its power when we talk about it (something I learned from Brené Brown).

What has helped is input from friends. One wrote:  “Thank you for sharing this. I’m glad you did. As Directors etc., we don’t share enough of the worries, the worthiness/unworthiness and the vulnerabilities that things like grants.... bring to the work and to our sense of ourselves as ‘good’ researchers, colleagues, leaders and people.”

She went on to say: “I wish I had great advice. I have nothing. Except that you are a good person, a good mentor.... and whatever happens, you will still be those things. If you receive the grant, you know what your work will be; if you don’t, you will have new and different work to do.”

She’s right.

It’s also true that a life in science requires resilience -- the ability to pick oneself up after a fall and to learn and improve from failure.  No one ever said that it would be easy.

In a few weeks, the summary statement will be released and I’ll start thinking (with my colleagues) about ways to address the reviewers’ concerns.  Until then, I’ll keep a space in my heart for these words of Samuel Beckett: “I can’t go on. I’ll go on.”