Life at the Roost: From Nano to Macro, “Cross-Talk” Signals Between Molecules, Cells, & Career Paths

An Interview with Theresa D’Souza, Director Of Development Services at RoosterBio Inc.

Listen to this Blog:

Carson: Friends and colleagues, it’s been too long, but we present to you another edition of “Life at the Roost.” It’s my pleasure and honor to introduce to you Dr. Theresa D’Souza, Director of Development Services at RoosterBio! Welcome to Life at the Roost!

D’Souza: Thank you Jon, and I’m really honored to be interviewed today as one of your cast members for the Life at the Roost. And I’m looking forward to having a bit of a chat with you.

Carson: Thank you so much. You’ve had such a richly productive career, full of scientific discovery as well as managing teams and helping bring new products to market. I thought I’d start by going back in time with your Nature paper with Professor Stuart Dryer. A lot of work seems to have gone into it… a lot of work that was leading up to that story. Would you like to “shine a little light” on how that came about?

D’Souza: I like the choice of words you have there. So it looks like you’ve done some reading on my research there, Jon! What took me to this “path of light,” if you will, was my love for neuroscience. That’s where I got into life science, and it took me to Dr. Stuart Dryer’s lab where we were looking at circadian rhythm, especially using a chick model. Called the pineal gland. It’s a really interesting model to study because the chick pineal is located much closer to the scalp on top, right? So the light can reach it—as opposed to humans where it’s more embedded. The function of the pineal gland is release of melatonin, and so it was a good model to study these pineal cells in tissue culture. My interest then was ion channels, because the basis of all our communication for our cells is the electrical network. The ion channels are an amazing part of it. So, the one burning question that we had was—using chick pineal cells as a culture model—was how do these ion channels get used in the circadian rhythm. This is where I’d done most of my work during my Ph.D. for the thesis, where I was in fact training the cells in an incubator and doing patch clamping in the dark or in daytime. Depending on what state the cells were in, you trained them in the day/night circadian rhythm pattern, studying the ion channels. That’s where the [Nature] paper was generated based on the findings. And an interesting channel was identified during that investigation.

Carson: That’s so neat! I cut my teeth on signal transduction early, myself, looking at a project with c-Src potentiation of the beta-adrenergic receptor with cAMP as the readout. So, all this “fast” [signaling] stuff relating to kinases and cycles…it’s so cool. I love it!

D’Souza: Yeah. In fact, phosphorylation was the main part of the investigation that led me to the next type of project, which was into my post-doc work… So, one thing led to another! That’s how the journey kind of goes in your career.

Carson: When you were a post-doc—for the youngsters out there just starting their academic careers—what might be some things to watch for when aiming for your best choice of post-doc experience?

D’Souza: It really depends on the individual, on their interests, and career path that they would like to move into. A post-doc gives you that window of a period where, even after you’ve done your thesis work, you may be thinking over going into industry or faculty or government or any other path that fits your interest… A post-doc gives you a little window with lots of opportunities to either hone-in on your current skills that you have—and use in another field—or you may go into the same field and acquire more skills. A post-doc is one of those career-navigating decisions that you can take.

Carson: Yep. You can branch way out—or stick to your old stuff—and become deeper or wider in your expertise. Only in this case with more autonomy, is that right?

D’Souza: That’s correct.

Carson: Related to your time at the legendary NIH, I see you advanced your expertise in molecular signal transduction towards new focus area—from neurology to cancer. So, broadening out a bit? Cancer signaling is where I started out at the benchtop, way back when… One observation that struck me is that when certain cancer cells are severely stressed by a genotoxic drug, they rev up NF-kappaB, perhaps blocking programmed cell death. Apologies for anthropomorphizing, but it’s almost like they’re trying to protect themselves! Crazy, huh? What were some things you found related to ovarian cancer and NSAIDs? Anything that surprised you?

D’Souza: This particular part of my post-doc that I did at the NIH with epithelial ovarian cancer… Specifically, we used a lot of cell lines, and it’s interesting to note with the NSAIDS—like aspirin for example—how that might diminish the ovarian cancer or some other types of cancers. There were some findings. At that time, ovarian cancers were not investigated heavily with the effect of NSAIDs. So that research showed that a transcription factor, actually E2F1, affects the cell cycle. It has an anti-proliferative effect. If it’s overexpressed, which is the case in epithelial ovarian cancers, the NSAIDs were found to suppress it. And so it inhibited the cell cycle. There were a lot of other molecular mechanisms to really narrow down to that particular transcription factor. It was an interesting finding! And it kind of confirmed what was also shown in other types of cancers.

Ovarian cancer is one of those cancers which is still really hard to nail the mechanism down very well. And some of my research also took me into tight junction type of work—that phosphorylation that I was trying to tie together with my Ph.D. work where one thing led to another.  So there’s my interest in phosphorylation mechanisms, and yet, it’s connected with a different field. You can see how it ties in with the post-doc decision as well!

Carson: Yeah. What doesn’t NF-kappaB do? Now there’s a question. Because you point out a whole other mechanism I didn’t even know about, really fascinating! […Switching gears…] What was it like working at NIH? Were you at the Baltimore site? I’ve heard it described as like a “mosh pit” by some people. Maybe not quite that way for you but…What was it like when you were diving into that environment?

D’Souza: That’s an interesting analogy you have! I think from outside the NIH, it can look daunting to people, but what I found is—having identified some of the key investigators where you’d want to expand on your key research work—I saw that NIH has quite a few of those experts with a wide amount of subjects to pick from. I didn’t really find it as a “mosh pit” because I believe I identified the right investigator whom I could work with (the ovarian cancer research). It was well-supported. The infrastructure is there, once you get in. They are looking for talent. As always, you have to have the right compatibility. Then it becomes a very interesting place to work in—because you learn a different world in some sense—but yet it is the science! We are all, at the heart of the matter trying to find the same things. It’s just a different setting.

Carson: Right. If I’d had another 10-20 years, definitely that would have been on my bucket list—work at NIH. Sounds so exciting. Then you changed scenes from to bucolic Walkersville, at Lonza. It looks like you really flourished there, advancing to lead teams of people. Is there anything about that experience that you still keep close to you and build from today?

D’Souza: Lonza definitely has expanded my horizons in different paths. I in fact had several roles. Within Lonza I worked with primary cells and media development. And then I had the opportunity to even do quite a bit of process development in cell therapy, including MSCs. And next I was given the opportunity to lead a team, a cell biology R&D Team, which supported the Lonza Bioscience—which has several products: primary cells and media. That was a very exciting time, and what I take from there is still of high value. It broadened my horizons and allows me to use the knowledge that I’ve gained from that work experience to where I am right now.

Carson: Right on! So everyone comes to RoosterBio from somewhere else, out from one door, in through another. Would you like to share what snagged you over here—what I sometimes call cheesily your “Rooster Journey?”

D’Souza: Well, as you know. As you know I’ve been on a “journey” for awhile in my career path. And in this journey I’ve decided to join the Roost. I just hopped in, and it has been a fantastic spot to be at! What brought me here was more from some connections that I had at Lonza, and second, my interest and passion for cell therapy, regenerative medicine. RoosterBio offers that to continue with that interest of mine. And that’s why I am here where I am, now talking to you, Jon!

Carson: A natural direction to grow in! I found the same thing when switching jobs over from this one company to, here RoosterBio, in 2020. It’s been wonderful so far. So now you’re a Director of Development Services. I admire everything you bring to our group AND your ability to communicate across teams, bridging customers and science to practical solutions aimed at the dynamic challenges of cell and gene therapies. Can you tell our audience a little more about what that’s like? And what is “Development Services”… for people who are new to RoosterBio?

D’Souza: RoosterBio, as I said, has its great depth of knowledge in our MSCs—and the regenerative applications of MSCs. Now we’re expanding more into the world of exosomes—because cells communicate, and their communication method involves a lot of output with these exosomes or extracellular vesicles. Given the fact that we have bright minds and great expertise in this field, we are well-positioned to support our customers with the services. Since we know our products, who better yet to help our customers to get them into the clinical, translational path than we? Because our products are very much focused toward translational medicine. Development Services allows us to use our products and also develop the customer’s process—and customize it—to get them to where they’re wanting to go with our help.

With that communication between RoosterBio and the customer, with that collaborative approach, we can employ Services to achieve that goal. To use Services, we have different paths. You can reach me, directly, of course. But we have our Sales/Commercial Team that can provide more input on some of our capabilities. Our websites are well versed in displaying these as well for the customer. Every project is different. Communication, talking with us with some set meetings, allows us to really understand the needs. As mentioned, we have a lot of experience with MSCs, but we’re also well-versed in the field of extracellular vesicles—and our capabilities are growing. We also have Analytics Services for not just MSCs but for extracellular vesicles as well. I highly encourage our listeners and readers to check our websites to get a little more understanding on each of these offerings.

Carson: Easy to navigate from! That’s right. So, what I’m hearing is that you take a lot of your knowledge of process development. And the customers, being experts in what they want to do, they need a bridge to help get there that’s somewhat custom-made. And then we help them cross that bridge to help them achieve the solutions towards scalability. Is it something like that?

D’Souza: Right. We have process development type of work where we can take customers from a benchtop, small-scale flask, right up into the bioreactors. And it can allow the customer to see that they may not be confined to a small scale. If they are trying to achieve large amounts of product at the end, a small scale will not be a solution—you have to scale up. RoosterBio has that capability; we have quite a few processes using our products already well established. We don’t have to start from scratch. You can come to us, and we can position you on a much faster path.

Carson: OK. And so, the [standard] Analytics comes in because we’re used to seeing the same types of assays applied to quality attributes. Is that right?

D’Souza: Correct.

Carson: And so, if you want to apply these [standard analytics] at smaller scale or larger scale—as long as they’re consistent throughout as you develop your process—then, well, is that how it goes?

D’Souza: Yes. Analytics is a very important component of this process. You are monitoring your process that’s maintained, and your analytics is your readout. Whatever the project may be, that will be important.

Carson: Shifting gears a little bit… Now here’s a personal question. Enough about work! What are some things Dr. Theresa D’Souza enjoys the most when leaving the office?

Theresa D'Souza

D’Souza: Well, as you said earlier, a city-to-bucolic move definitely has struck a chord with me. What really gets me going—literally(!)—is gardening. I love the area where we are, just love to be part of nature. I have a lot of other interests, but gardening I think is at the top, at this time.

Carson: I hear ya. Love growing stuff, too. Just this year I tried to grow a bunch of potatoes. And worked actually!

D’Souza: I did too, actually, for the first time.

Carson: They just like to grow! I used some pine needles and compost and soil, mixed them together. Just doing experiments. It [gardening] is a big laboratory, you know?

D’Souza: I may add that our “Roost” has several people who are into gardening, so it’s a lot of love of science and love of nature combined at this place. And the sharing that goes on is really excellent.

Carson: Here’s another question. It’s Fall, now. Autumn in Maryland. I love this season—probably my favorite—for no particular reason other than the “vibe.” Are you also partial to autumn, or are you more of a winter/spring/summer person?

D’Souza: Absolutely autumn! I’m an autumn person and you know, our “Roost” feels like autumn year-round with all its warm colors. I feel like I’m in the season throughout the year which is great.

Carson: Bright blue-n-orange skies with orange trees… It kind of fits our color scheme.

One last question, the obligatory silly one, I cannot resist. If you could be a Star Wars character, which one do you think you would choose to be? Or perhaps, which one would others choose for you?

D’Souza: I think I can see myself more as Rey or Leia?

Carson: Yeah! I can definitely see that. That’s very cool. I don’t know what character I’d be, probably Chewbacca, because I wouldn’t have to talk much. [chuckles] Are there any questions you’d like me to ask you that I may have overlooked?

D’Souza: I don’t think so. You’ve almost taken me back in time, Jon, down my career path. This has been a great introspection, you might say? So I thank you for taking me down this and I’m glad our paths crossed here. I appreciate all your insights as well that you bring to Roost.

Carson: OK. Thank you so much! I think that’s probably a wrap for this interview. Thank you so very kindly for joining me. I really appreciate it.  Wishing you and everyone happiness and wellness until next time!

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