Town Hall: Research’s changing landscape

Unknown Speaker
Okay.

[Dean Joe Guglielmo, PharmD]
Welcome everybody to the September School of Pharmacy Town Hall. Before we get started, I'll give you a few tips. As usual, your audio and video will be automatically muted and only the panelists can unmute themselves. Please note that the chat function is disabled. If you have questions, please use the Q&A feature. As always, any questions that we're unable to answer during the town hall will be answered in email or if anonymous at the next town hall, and we'll hold all questions until the end. So as usual, I'm going to start with a little bit of data as it relates to the Coronavirus. There's a lot more to discuss as well. But just to center us on the statistics at the moment and utilizing again, the University of Washington database and predictor, the at the moment, they give one of three potential predicted outcomes by January 1 in the way of deaths. If things continue as they are nationally, the estimate is that the current that the deaths, doing things the same way as we are now, will be 408,000 deaths in the US. However, if people adhere to using masks when appropriate, that figure drops to 286,000. And if the mandates that currently exist are eased, actually, that total goes all the way up to over 600,000. If you look at daily deaths, they do a similar sort of analysis and that is at the moment, they predict that it'll be about 25 or 2,600 deaths per day. By January 1, but if masks are used that drops below 2,000. If the mandates are eased, that total goes up to over 12,000 deaths per day. In the case of California, at the same sort of analysis, if things continue as they currently are, they anticipate 50,000 deaths by January 1. However, if mask are adhered to it drops to 32 or 33,000. But if the mandates are eased, it goes all the way up to 72,000. There is some good news. It's clear the cases per day in the San Francisco Bay Area decrease from what was approximately 2,000 cases per day. And that was like late July, early August. And that is now to say just slightly over 500 now. Deaths are decreasing from what was a peak of above 80 deaths per day and late August to now, what is low, below 10. And just for the record, as of right now today, the number of cases and UCSF hospitals are down to 23. And it was up over 40 there for a while. But I will say it's not just Coronavirus. We continue to have the racial injustice that exists in the United States and beyond, global warming, the West on fire, it goes on. The only comment I would make here is, please stay positive. This is not a time to be passive, and to assume there's nothing you can do be an activist in any way you potentially can.

And one activist role would be November 3, please vote and please vote earlier rather than waiting until that day. There are a few campus updates that all relate to a lot of what's been going on with Coronavirus and beyond. You probably know now that there is a UCSF COVID-19 Relief Program. The chancellor has announced this program for UCSF employees making $75,000 or less who are facing financial hardship during the pandemic. And as similar programs available to UCSF students seeking financial assistance and discussion with Dan Lowenstein earlier this morning. We know there has been a lot of interest in taking advantage of these potential relief programs. In addition, the work from home guidance has been extended through June 30 of 2021. And there, they've extended this guidance for all employees who can perform their university duties remotely. They've also created free by UCSF and tele kit toolkit includes guidance for employees who are working remotely and you can find that online at the Coronavirus hotlink. at UCSF. I will remind everybody, as per the office, the president once again, everybody is required to have a flu vaccination, UCSF will start providing influenza vaccines to campus flu shot clinics, starting this particular week, with the hope that everybody is vaccinated by November 1 once again in compliance with the Office of president's executive order. I've said this before and I'll say it again, the shots are particularly important to get this year, to help reduce the anticipated burden on our healthcare providers and health system during what could be another exacerbation not only of influenza, but COVID-19 as well. As a reminder, this vaccine is still required if even if you're working from home and other remote locations. If it's more convenient to get the shot from a local provider near you, please do so. And that's probably enough for me. I want to kind of move into what is really our topical program today. And this relates to the how Coronavirus has just changed the landscape of how we do research. And to that end, I will be passing the baton to the Associate Dean for Research in the School of Pharmacy, Dr. Andrej Sali, who will host reports on this topic from a number of individuals that he will introduce to you, Andrej.

[Andrej Sali]
Thank you, Joe. Hi everyone. So we thought that we would invite, we'd have three slots, four minutes each that will be divided between Klim Verba with a little assist from Jacqueline Fabius claim is fellow at the QBI institute Jacqueline is the chief operating officer. They're the right hand of new incumbents. They'll be followed by Rosa Rodriguez from Clinical Pharmacy. And then Jaime Fraser will finish off that series he's in BTS. In addition, Fran Aweeka will give some concluding comments perhaps looking into the future, trying to encourage you to share your thoughts about maybe the bad aspects of doing research in the COVID area at the level of PIs we felt as opposed to students or postdocs, or staff this time around, just trying to encourage everyone to maybe come up with their concerns and plans to address them. Thoughts about it, and maybe we will have more conversation along these lines in the future. So now without any further interruption from me Let's have this presenters claim or Jacqueline.

[Kliment Verba]
Sure one second. Let me share my screen. Can everyone see my screen? Yes.

[Jacqueline Fabius]
Okay, so today we wanted to tell you about QCRG the QBI Coronavirus Research Group and the formation of the QCRG was really the understanding of the context of a coming pandemic and taking action. It was a rising opportunity to start to change how science can be done through extensive collaboration and lead to rapid advancements. 42 labs at UCSF came together to research COVID-19, each bringing their own expertise to address the problem. This meant that hundreds of scientists were working together over zoom at this time, which became quickly unmanageable, and therefore quickly broke into subgroups, each of which with a focus Klim Verba, as Andrej mentioned is a QBI fellow and one of the leaders of the structural biology subgroup, and he's going to tell you about their swift success.

[Kliment Verba]
Thanks Jacqueline? Yes. And so, you know, as a structural biology subgroup, our goal the scientific goal has been to really bring some sort of atomic level molecular understanding into the viral infection. And as a starting point for, you know, on the journey, we use this as a protein protein interaction map, which was the first paper which came out from QCRG, where all the post viral protein complexes have been identified, where you know, the viral was a virus infected cells, and then it interacts with all this human proteins in our own cells to either hijack them or just protein strike to fight the virus. And so having this list is amazingly important that's useful, but without having their molecular structures is not in the standings, the exact atomic details of how this proteins come together. It makes it very difficult to design therapeutics drugs and understand the mechanism of how this is this works. And so our the goal of our group, the broad goal of our group is to really bring electro details, disease interactions. And you know, many people over all over the world scientists really came together to produce a number of high resolution structures or viral proteins. But many of the viral proteins by themselves are still not visualized, and furthermore, is the complexes between the host and the viruses. Most of them are in a dark visit. To my knowledge, there's basically one structure between the host viral complex. One thing which was very apparent from the beginning is this is a huge effort where you were talking about 50-60 structural targets. And so when Oren Rosenberg a faculty here at UCSF and I were tasked with meetings as structural biology subgroup, it was clear that no single lab can really, really attack this And so what we did is we went ahead and actually made a call to just the general structural biology community at UCSF, asking people what, who would, you know, in the trainees and postdocs, anyone who wanted to join really, who would like to be part of this effort to structurally understand how this forest works. And what has been amazing is that over 60 volunteers came up and said, yes, you know, I would like to help be a protein expression or purification or structural refinement, anything that as a scientist, you know, this are incredibly well trained scientists, incredibly smart people wanted to help and do this together. And what was really cool also about this is that they all came from many labs, many departments, it was really sort of across many buildings, even across UCSF effort. And, and this is this is always a scientific meetings looked like during the COVID-19 research. And so once we had this amazing group of individuals from all this labs. The next question was how do we really organize this group so that they we can work efficiently together. And what we came up with was really organizing it by functional subgroups. So this is probably much more akin to how one would do things in the industry or as in canonical academic approach, where we had a leadership group which would help us make more strategic decisions of what to do, but then each of the other subgroups would be 10 to 20 trainees and each subgroup would be tasked with a specific function in expression purification, different structural techniques or data processing, and each group would have a faculty leader who would oversees a zonal process. And then also what we have is we have this team leader positions for the trainees, whereas they oversees everything, they help with the every day process in the team and also they get to incredibly, incredibly important mentorship experience. And so this has been great. But the question is, does this work? And so and it does, so we started from zero in, in April. And here's this is not published yet, but this is something very exciting to us, we got this couple of weeks ago. This is a structure of a human chaperone interacting with a viral protein and then green is this chaperone. And in the orange, this new helix was loop sticking out is a piece of a viral protein which we basically pulled out from the protein-protein interaction map and followed up and we were able to obtain the structure and we can already see but then come up with mechanisms, how it might be working based on the structure, and potentially the structure can now be used to develop therapeutics etc. And this is just one of the structure success stories in the past couple months. We are also in a right corner of a slide you see we've had a number of amazing collaborations with Aashish Manglik and Peter Walter's lap and Jim Wells' lab on nanobodies we were able to quickly leverage this group of individuals to a to z expertise to really apply for grants and got three grants to do science and more is coming. So I think this you know, has been an shows incredibly well what can be accomplished when a group of motivated excited, and very competent people come together to do science together. And that's it.

[Andrej Sali]
Jacqueline, do you have more to say?

[Jacqueline Fabius]
No. Congratulations.

[Andrej Sali]
Okay, good. Rosa, would you go next please?

[Rosa Rodriguo-Monguio]
Yes, of course. Thank you very much for the opportunity, on behalf of the Medication Outcomes Center team, to share with you some of the preliminary data, a pharmacoeconomic study we are doing in COVID-19 patients. We... an observational retrospective study design, using EPIC electronic medical record data and following patients longitudinally. The primary study aim was to assess medication administrations during hospitalizations, and related outcomes and treatment cost. And we included a cohort of COVID-19 patients and a comparison group, patients with human influenza diagnosis.

[Rosa Rodriguo-Monguio]
The study included both population groups, pediatrics and adults, who tested positive for COVID-19. And as I mentioned, a matched cohort of influenza patients. Patients have to be at least 24 hours ... at the UCSF Medical Center. And the first data pool that we have goes from March 1st through June 30th, 2020. Our primary study outcome was in the hospital mortality rate. And in addition to that, we looked into the length of the stay, the ICU admission rate, ICU, intensive care unit length of stay, drug [...], and the treatment cost. Some of the preliminary findings in the four months of data that we have so far, there were 508 hospitalized patients, corresponding to 493 unique patients. So 508 encounters with 493 unique patients, meaning that we have patients that were hospitalized more than once during the four month study period.

[Rosa Rodriguo-Monguio]
Of them, 7.9% were children. And among these patients 64%, almost two thirds, of the patients were male of the COVID-19 patients were male, compared to 45% of the influenza of patients who were male. To begin points before, we observed that 35% of the COVID-19 patients were white, while 90% of them are Black or African Americans. So in other words, the incidence of the COVID-19 disease impacted, it was two times greater among the African American community than the white patients. The mortality rate was 3.7% on COVID-19 patients compared to 1.3% on the influenza patients. All were adults. The variance of the length of the stay of the UCSF Medical Center was 10 days, over 10 days, for COVID-19 patients compared to three days for influenza patients. And the difference in the length of stay and intensive care unit admission rate between the two groups, the COVID-19 and the influenza patients, it was also statistically significant.

[Rosa Rodriguo-Monguio]
What we have observed, in the preliminary data, is that hospitalized COVID-19 patients use a wider spectrum of pharmaceuticals, including inhalers, bronchodilators, antivirals, antibiotics, neuromuscular blocking agents, sedating medications, opioid anesthetics. So the preliminary evidence shows that COVID-19 hospitalized patients may go under a lot of significant clinical and economic implications not only for the patients but the families. And certainly UC health enterprise.

[Rosa Rodriguo-Monguio]
We recognize and are very grateful to the large effort in other way their forms, both the institution and certainly the school. And we're very grateful for the department support to grant us access to these data. Some of the challenges that we encountered, and some of the opportunities that we've seen moving forward, relate to common challenges working with big data, such as timely access to patient level outcomes data. Data messiness is another challenge and the lack of comprehensive community data. Thank you.

[Andrej Sali]
Thank you very much. Jaime, you're next.

[James Fraser]
Hi. So I'm going to update on a charge that Andre asked me to, which is, you know, how is COVID and the work from home period affecting the way we do research, not so much my research program, because I'm involved in the effort that Klim outlined. I think that's been super important and energizing. But it's really, you know, changed a lot of the questioning that I do for myself about how I run my research group and how we should be running research groups.

[James Fraser]
Running a research lab is kind of a weird thing. I think the closest analogy is that it's kind of like running a franchise of a fast food restaurant. We have a shared infrastructure, but each lab is relatively independently as far as budget and personnel. And that is wonderful because there are many different styles that can evolve through that. But it's also really hard when we need to communicate things like a lab shut down, and different policies. And then when you add on top of that, on top of the pandemic, the ongoing crisis in racial justice that we're having in this country, it's been a really challenging time to think about how this is affecting researchers, or the process of research, and how work and the ability to work is being distributed. So we're thinking a lot about what are the strategies that will enable us to lead our groups effectively, in an equitable manner and in a transparent manner, and that transparency needs to go through all levels from above the individual lab level all the way through through the lab.

[James Fraser]
So I've been trying to think about that question and a lot about what will we do differently next time? And I don't know that there are that many concrete things that we could do differently next time other than an increased focus on transparency. There are no easy answers and there are no quick fixes. As we've been reopening, you know, how has the communication gone? Should it be going through departments, graduate programs, the lab neighborhoods, through the School of Pharmacy, School of Medicine? You know, it's been really confusing and, and it's been unclear for us sort of what truth is and what's coming. Even though I know people have been working hard on trying to communicate transparently.

[James Fraser]
Then once we started running our groups, how do we allocate time in lab? We're trying to work safely at lower capacity. How does that work with training people when you might need to be in close contact? This is uncharted territory. We don't know what we're doing yet, and we're trying to figure it out. And how do we find ways to share what's working between different labs? What is this going to mean to outside evaluators? That's a question that's bothering us. You know, we're already seeing disparities by gender or caregiver status. And this is putting people in an impossible situation of choosing between safety and going into lab and being productive.

[James Fraser]
Moreover, you know, how do we accommodate caregiver responsibilities at all? There's no school. I've felt this myself. You know, I have young kids, they're now back in UCSF daycare. Do I feel like that daycare is safe? I don't know. Their YMCA learning camps being run? Are they safe? We don't know. You know, I think that every effort is being taken. But it's, it's really hard. And just because people are sending their kids to these situations doesn't mean that you feel completely comfortable doing it. And that's a really hard position.

[James Fraser]
How do we give space to people in our labs to grapple with societal unrest, racial inequality, the mental health strain of the fact that nearly 200,000 people are dead. You know, we got to listen to our, the people in our lab, I'd like to give a special shout out to the folks in my lab who teach me a lot. But I think lab leaders also need to take responsibility for leading these conversations, and for their own self education.

[James Fraser]
So now, I feel like we're in this next phase, but why are we in a next phase? Nothing has changed. Everyone is just restless and the sky is freaking orange. How are we going to increase capacity even more? And how are we gonna do it safely? I don't know. I don't understand where we are on testing or communication of policies. You know, I'd like to see a lot more transparency on that end, and I know that people are working hard on it already. So to those people who are working hard on it, thank you. Thank you to the staff who are keeping things running in labs, the custodial and security staff. Thanks to everyone who's working so hard keeping departments and schools afloat from home. We appreciate you. And I know many people are having a tough time. I'm having a tough time too. And it's great to gain strength in a community like this. Thanks.

[Andrej Sali]
Thank you, Jaime. Thanks a lot. And I am guessing this is going to transition reasonably nicely to Fran's comments, Fran.

[Fran Aweeka]
Sure. Thank you, Andre. Yeah, there'll be a little bit of overlap with the points James made, but maybe I'll be posing a few questions. I thought that after hearing the inspirational science talks by Klim and by Rosa, and then I don't know if you had a chance to listen to Aashish earlier today at the School of Medicine grand rounds, but it was outstanding. I don't know, Aashish, if you're on but in the q-and-a with Dr. Walker was, I think particularly strong, so we're really proud of you. All the science going on in the school.

[Fran Aweeka]
But I thought maybe I could just start by giving a little bit more of an update of research in the Department of Clinical Pharmacy. I think what's true for all the departments is that established work is steadily moving forward, and perhaps a slower pace. I know that our main laboratory is almost at full speed. And our clinical trials nationally, internationally are starting to recruit. I know internationally, we are pretty active in Africa. Nationally, the essential trials are moving forward, the non essential trials actually are having some challenges. So there's things are not quite revved up. But again, established work is moving forward. And there have been, you know, generally established funding, I think, looks pretty good. There's been a few issues that have been brought to light in terms of one five year grant that was doing great for two years, and then there were some issues with the third year funding, which hopefully I've resolved and then a particular grant where it was really borderline, a new grant and I think before COVID, we feel very strongly it would have been funded. But because of COVID, or blaming it on COVID anyway that it didn't quite get funded. So funding is generally okay for established work, but for new work, we're concerned.

[Fran Aweeka]
But I wanted to follow up on what Andre said, I would say, and then a bit of what James was saying. And that is to try to initiate some discussion, hopefully here and maybe in a future Town Hall, on how COVID has impacted how we do research, like James was saying, but then also our satisfaction with our work, which also was alluded to. And you know, to state the obvious if I may, for a moment, I think we all agree that Zoom discussions, meetings, our teaching I mean, it's really quite effective. I don't know what we would do if Zoom didn't exist. I think we all feel we've been relatively productive that way.

[Fran Aweeka]
However, at least from my perspective, it's the in person interactions that we have really, always found so stimulating and has made work fun, that obviously are on hold. It's the inspiring in person seminars, and the face to face research and committee meetings where ideas can be more casually shared, and new ideas can be more naturally generated. I mean, all those things are definitely being stifled by what's going on right now. And so not to state again, too much the obvious, James already pretty much has stated it, you know, is this truly compromising our scientific progress? Is it compromising our motivation as faculty, as students, as staff? And I would say it is, and what can we possibly do about it at this time.

[Fran Aweeka]
But in addition, as James also alluded to, it's the inability to separate home from work. And I don't know about the rest of you, but that was always really important for many of us, certainly important for me, especially those of us have school aged children at home. But for anybody, being able to separate home from work is part of what makes work fun. And then you come home and you have fun at home. And now we really it's kind of all blended together, and it brings a lot of distractions to our ability to get our work done, and to be really present for our work.

[Fran Aweeka]
So anyway, I'll leave it at that. We're interested in knowing what you think, and how it's impacting science and work satisfaction, and how we might possibly be able to address it. I had this great idea, I was at Mission Bay on Tuesday, I thought, oh, look at all this space. But then I listened to Monica, Dr. Rutherford, and then Joe. And of course, I think our ability to actually resume in person sessions, even if masked and even if small, may be somewhat limited. But is there something we can do to try to recognize, you know, first of all we need to recognize this is going on, but then how can we probably address it? So anyway, I'll leave it at that. I'll turn it back over to you, Andre. Thank you.

[Andrej Sali]
I'll just quickly say, thank you so much to everyone for their comments. Maybe the only other thing I'll say is that everyone was explicitly asked to please bring up any research problems, any group leadership problems, any institutional problems as much as they could, problems, things that we could improve. And you saw what the presentations were, there were not that many problems, despite the invitation. And so I would almost take that partly as a positive sign, partly as a sign of people perhaps having to be encouraged to speak up sooner rather than later. So please don't inhibit yourselves. PIs, if you have issues, maybe systematically transmit them to your chairs or to the dean or even to me and we can then talk about them and try and do something about them, especially if they seem to be at the level of the School of Pharmacy as opposed to the planet or the country as a whole. Thank you. Probably Joe, you want to say something?

[Joe Guglielmo]
I thank you. Thank you, Andre. And thank you, Klim, Jacqueline, Rosa, Fran, Jaime, I appreciate the comments. It was really fantastic. And I do think there's a lot of opportunity to expand on what we have discussed and to get into great deal of more depth. With that we are a little bit past the hour. And so I, as always, I will close saying, please take care of yourselves, particularly during these times, and it just seems like it's compounding one thing after another. Do your best not to let it happen to you, be activists, and I'll repeat, November 3 is coming. Please vote. Until next time, please enjoy the rest of your afternoon and thank you all for this participation.