A Great University engaged in Drug Discovery: University of Pittsburgh
Reporter and Curator: Larry H. Bernstein, MD, FCAP
The US-based pharmaceutical companies have been consolidating and now are moving offshore to reduce taxes and other costs. A part of the problem has been the large cost of clinical trials, the failure to detect toxicities in the early phases, and late phase failure or drug resistance conferring short term success. This has been at a rate above 60%. The result is that Big Pharma is looking to recycling old drugs for repurposing. Whatever success can be obtained from this, there is a larger problem in not having a comprehensive biological understanding of the problems imposed by the complexity on a deeper understanding. I present here a major university, very well recognized in genetics, proteomics, and experimental pathology engaged in the drug development effort with reasonable promise of successes.
Perspective On: A Drug Discovery Lab
As lab manager at the University of Pittsburgh Drug Discovery Institute (UPDDI), Celeste Reese and her team use high-content imaging strategies and work with many other labs both within the university and outside the university on a wide range of projects.
By Rachel Muenz | July 03, 2014
We try to use new technologies and approaches and quantitative systems pharmacology (QSP) to complement the traditional drug discovery strategies
Finding Clinically Relevant Solutions
Hard work, teamwork, and a whole lot of multitasking help this lab overcome a tough economic environment
“We try to use new technologies and approaches and quantitative systems pharmacology (QSP) to complement the traditional drug discovery strategies that are used by the large pharmacy companies,” she explains, adding that, on average, they have seven to ten active projects going on at any given time. “Right now we have a metastatic breast cancer program, a head and neck cancer project, and a Huntington’s disease project. We do some zebra fish modeling, some development of novel HIV diagnostics, liver modeling, and a variety of other things.”
Those projects take place in the institute’s 11,000 square feet of space, which covers two floors of the building the institute occupies and includes a large open lab on the top floor and an imaging lab, automation lab, and tissue culture facility on the floor below. Working in that space are 34 staff, including seven faculty, four graduate students, and five undergraduates, with the rest made up of technical specialists, administrative staff, and Reese herself. As in many other labs, staff members have a wide range of education levels—from high school for the undergrads all the way up to extensive post-doctoral experience for the faculty, Reese says, adding that staff receive quite a bit of training when they begin.
“The university has a lot of training modules that we send people to for such things as chemical hygiene, safety, and blood-borne pathogens, even things like safe shipping,” she says. “Then there are modules like conflict of interest training and research integrity training, which are also provided by the university. In-house, we train everyone on our equipment and on the procedures and protocols that we use within our institute.”
Training the grads and undergrads on those lab procedures is a big part of Reese’s role as lab manager, a task that she considers one of the highlights of the position.
“I really like working with the graduate students who come into the lab,” Reese says. “They always have a fresh perspective and they’re always challenging established protocols. They’re fresh and enthusiastic.”
The Catalyst Express robot is used to load plates onto a high-content imaging platform.It was a similar enthusiasm for science that led Reese to pursue the field in university, which led to a job in a pharmacology lab after graduation, getting her interested in the drug discovery field and—after 14 years staying home to raise her children—eventually brought her to the UPDDI, where she has worked for the past eight years.
“I’ve always loved science in general but then after college I got the job in the pharmacology lab and I just really liked experimental design and problem solving and implementation—which eventually led into the lab management position,” says Reese, who has now been lab manager at the UPDDI for four years.
Because of her enjoyment of experimenting, along with her other management duties of looking after supplies and equipment, Reese also likes to keep a hand in what’s going on in the lab.
“I keep an active role in at least one of the research projects that we have going on,” she explains. “I find that that’s very helpful in the lab management area as well, because I see key things while I’m doing experiments that I normally wouldn’t see on a walkthrough.”
Blocking out the day
Liquid nitrogen cell bank.
Liquid nitrogen cell bank.For Reese, scheduling chunks of time for certain tasks is critical in ensuring she meets her goals for the day.
“Time management’s key when you’re trying to cover as many roles as it takes to do this job,” she says. “I try to keep the mornings for the lab management tasks and then the afternoons are usually taken up with meetings, experimental design and implementation, or data analysis.”
That means Reese’s mornings typically involve coming in, checking on what’s happening in the lab, looking after the ordering of supplies for the week, and attending to any equipment problems and emails. Along with meetings, her afternoons are usually taken up with running or designing experiments or analyzing data. Of course, the rest of the staff have a variety of different roles.
A few programs and regular inventory checks help keep everything organized.
“One of the big tools we have is a purchasing program that we have developed in-house—an access program that we use and a similar one for equipment reservations and things like that,” Reese says. “We do a weekly inventory. We have two stockroom areas and we have two student workers who go out and stock all the individual work areas for people every day. And then we also have written protocols and established procedures for things like routine equipment maintenance and buffer preparations and such.”
She adds that the main challenge her lab faces is the same one that many other labs face—doing more with less in the current tough economic climate. For her lab, multitasking and teamwork are a big part of solving that issue.
“We just have really talented people here,” Reese says of her staff. “Everybody takes on a variety of roles. Everybody pitches in with things like routine equipment maintenance and … rather than having one person in each job, everybody covers a variety of tasks.” Because of that strong teamwork, Reese finds she doesn’t need to do much to motivate members of the lab.
“I don’t manage people—I just try to lead by example and try to take care of any issues that come up promptly rather than put things off,” she explains. “Everybody’s pretty self-motivated and hardworking here.”
An automated compound storage system is used to store the institute’s screening libraries.
six separate tissue culture facilities
| An automated compound storage system is used to store the institute’s screening libraries. | The UPDDI has six separate tissue culture facilities equipped with biosafety cabinets, incubators, and microscopes. |
The tech side
Along with the aforementioned high-content imaging, Reese’s lab also uses automated liquid handling platforms, biosensors, microfluidics, and immunofluorescence and fluorescence microscopy, and they are starting to implement 3D cell culture strategies to tackle their many projects.
“These fluorescent proteins react to the physiological changes in the cell in real time,” Reese says of the lab’s work with biosensors. “And [with] microfluidics you actually have a moving system. The system is more clinically relevant— it’s a better model for the in vivo systems.”
By “clinically relevant” Reese says she basically means the center is trying to more closely model what is actually going on in the human body, rather than relying on traditional 2D cell culture models or high throughput methods. That focus on clinically relevant methods is a result of big changes in the pharmaceutical industry in recent years.
Top 5 Instruments in the Lab
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“In the drug discovery field in general, big pharma has been using the mass-scale high throughput screening for a long time and of course now we’re coming to the patent cliff for a lot of the pharmaceutical companies, when a lot of their moneymakers are going off patent,” Reese explains. “So here, we’re trying to move away from that high throughput screening toward a more high-content [screening] where we’re looking at more clinically relevant methods and QSP approaches for drug discovery.”
And the most interesting work the lab is doing right now?
“I would say the coolest thing we have going on is a liver microphysiology project,” Reese says. “We’re making a liver biomimetic, which will be integrated with other organ biomimetics to create a human-on-a-chip for use as a model for drug toxicity and other kinds of organ analysis.”
Categories: Research-Specific Labs
Tags: Drug Discovery Labs
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