Kathrine

Thank you for joining me today. To start, would you mind introducing yourself, your field, and the main questions your research group studies?

Professor Huang

So my name is Rong Huang. I'm a professor at Purdue University College of Pharmacy. So my lab mainly focuses on discovering the novel drugs for under-explored targets.

Primarily we focus on epigenetic drug discovery.

Kathrine

Mm-hmm. So thinking back, what made chemistry, biology, or pharmacy genuinely interesting to you?

Professor Huang

I cannot recall specific items. I think the main thing I was driven to the pharmacy field is when I was in high school, one of my best friends, her parents died of cancer. At that time, cancer is more like the death sentence.

So I think trying to see if we can use our knowledge to discover a new drug to make a big difference in the patient's life and also their related family members kind of life, that's probably one of the major driving force.

Kathrine

Can you walk us through your path from university to becoming a professor and then eventually leading your own research group?

Professor Huang

So, I mean, the path is not a straight line. So it started with my trying to discover the new drug discovery, but I think at that time I was naive. So I went to the Tongji Medical University School of Pharmacy.

So I did a bachelor degree in pharmacy. So it's more the pharmacy here. But then through those coursework, I don't think I learned how to discover drugs, but you get some foundational knowledge.

That's mainly the undergraduate research. So then kind of to continue the study, I also did my master's degree there. And then so I learned more.

And then I began to instruct there for two years. But still, I think at that time, the equipment or the hardware in China was not that great for any junior researchers to do really meaningful research. So that's kind of promoted me to pursue the PhD in US.

So I mainly focus on the school pharmacy because the driving force is the drug discovery. So I joined the Purdue University College of Pharmacy Department of Medicinal Chemistry and Molecular Pharmacology. So it's kind of unique department combined the chemical synthesis to design a drug and also to test a drug in one department.

So there's a lot of collaboration among the faculty members. So I think my PhD research is mainly to site specific, deliver some novel drugs to the tumor. I think that's the reason I joined the lab.

So then I did, I think over the five and a half years, I did probably 90 percent is the synthesis. And then towards the last semester, we finally got all the compounds synthesized that we need to test. At that time, we cannot find any labs help us to test.

I have to learn everything myself. So through that process, I learned about chemical biology is quite different from chemistry. Chemistry is a black and white.

So from the characterization, the LMR mass spec, you know whether you've got your compound or not. But for the biology, you never get the same result. So that was frustrated by that.

So I thought, oh, I need to learn more on the bio side. As I went to Johns Hopkins, did my postdoc with Dr. Phil Cole. So there are many more about chemistry and some kinetics, purified proteins, and also continue to do some protein chemistry.

So I don't know, unlike some other scientists or faculty member, they know they are determined to be the faculty member professor. I always kept my mind open. So I just want to, I kind of explore all the different paths.

And eventually it turns out to be being a faculty member, maybe my destiny. So I started my independent position at the Virginia Commonwealth University School of Pharmacy, Department of Dental Chemistry. So being a faculty member is very different from the being a postdoc, being a PhD student.

Because when you are trainees, you are mainly to really do the job, do the bench work, do the experiment. But being a faculty, things you never learn is how to manage people. So that is one of the big challenges, I think, for most of the faculty members.

Because everybody thinks different. So even the trainees, they may think different from what you think. So you have to understand them, be able to communicate.

And also, of course, writing the grant to obtain the money to support the research. That's another big hurdle. So I think, but then you kind of learn along the road.

And then with the teamwork, either through the collaboration or through your trainees, I think we eventually was able to secure the grant and then publish the paper. So then I hope to, after I stayed there for six years, I decided to move back at Purdue. So I've been here nine years now.

Yeah.

Kathrine

So your lab studies protein modifications such as methylation and acetylation. Could you explain what those are?

Professor Huang

So methylation, you guys learn the chemistry, right? So methylation is one carbon with three hydrogen. So it's very small modification.

Acetylation is two carbon, one oxygen, three hydrogen. So using the example, it's like the protein itself does not change. Then you just attack different things on the protein.

So through this tagging, then you may recruit additional protein to recognize this tagging. So then it will either transduce the signal to the downstream or have some other conformational complex to carry different function. Using example, I think maybe you guys like to use the sticky note.

So the document itself is like the protein that you put at different sticky notes on your books or on your PDF file. Those sticky notes are more like the methylation or acetylation. So when you look at a sticky note, people may catch different sticky notes.

So those information may be translated differently or transduced differently.

Kathrine

So what specific research project is your group working on right now? And what are you trying to discover?

Professor Huang

We have multiple projects ongoing. I think central theme, as I mentioned, is the drug discovery. So I mainly focus on the methyltransferases that are mainly responsible to install the methyl group either on the different proteins or on the RNA or DNA, or even small molecule inhibitor.

Another project is the acetyltransferase, so the enzyme that mainly responsible to install acetylation on the proteins. So does that answer your question?

Kathrine

Yeah. Next, could you walk us through one completed experiment or discovery from your research?

Professor Huang

So maybe use one of the methyltransferase as example. So we start, that enzyme was just discovered in 2010 in the pneumonia cell. So I started my lab in 2011, so only half a year ago.

So I started, so my research mainly always focus on a more curiosity-driven. So I want to do something no one has done. So this enzyme is new, and then this modification has been very conserved from the bacteria all the way through the human.

But there's many things we don't know. So we started this project. What we did is we obtained the plasmid, then we did a purification from the E.

coli, and then we designed the assay trying to monitor the activity of this enzyme. So then we understand how this enzyme work, either it's bind to one substrate first, and then bind to the second substrate, or we call the cofactor. So there's no preferred sequence that really needs the product.

And then in the meantime, so we collaborated with the structural biologists to try to understand how this enzyme recognizes the substrate peptide, and we did some mutagenic studies. So by changing the peptide sequence or changing the sequence of the protein to really understand which interactions is more important. From there, based on the structure or connected mechanism, now we did two rounds of the rational design.

So one design is to mimic the transition state during this catalysis. So we'll be able to obtain the nanomolar inhibitor. Also from the structure understanding, we were able to convert the substrate to the inhibitor.

So those are probably one of the story. So by understanding the basic science, now you'll be able to apply what you learn, and to be able to kind of make some molecule to integrate what you want to achieve. In this particular case, we want to inhibit the catalytical activity.

Kathrine

Yeah. So next, what does a typical day look like for you? And how is your time divided between teaching, meetings, writing, mentoring, and lab work?

Professor Huang

So it depends on whether I have a habit to teach or not. So most of my teaching are in fall semester, and I teach two courses back to back. So when that occurs, it's pretty busy with all the teaching duties, because then it's every Monday, Wednesday, or Friday.

So even though I have been taught this course for almost 10 years, but before each lecture, you still have to refresh your mind to see, incorporate any comments you got from the previous year to see how you'll be able to help the student understand better. So that teaching, like the teaching itself lecture is only one hour, but most of the time is spent to prepare the notes, and also to come up with the right questions to test the student's skill. So if one lecture time, at least it would be four to five hours total for that particular lecture.

And then you have to, we have to give the office hours so the student can ask the questions and some of the administrative work, like reply to emails. So when the teaching is on, the time are pretty limited. So then normally Monday, Wednesday, Friday, probably most of the time is related to teaching.

And then Tuesday and Thursday, then I can have some time for the research wise is I meet with my lab members, everyone, every week, between 30 to one hour. So we go over the what they have been doing, what problems they encounter, how we're going to solve these problems. It's kind of the troubleshooting and a re-prioritize the goal.

And then other time is writing a paper, meetings, committee meeting, or some other service meeting. And also review the grants, or write the grants, or talking with some collaborator, either initiate a collaboration or discuss what is the update. Yeah.

Yeah.

Kathrine

So earlier, you mentioned that you felt like you were destined to become a faculty. So I want to ask, how did you know that academia was right for you instead of going into something like the pharmacy industry?

Professor Huang

Now, as I mentioned, I'm unlike some other faculty member, I'm less committed at the beginning. Actually, I try to avoid to go to the academia, which may be a surprise, but I keep my mind open. So through your process, if you know what you want to do, it's good.

You have a clear kind of milestone you want to achieve, to achieve your goal. But if you don't know, you just really focus on what you are doing now. So you just ensure you'll be able to learn things well, troubleshooting the process, independent thinking.

What I said, my destiny is meant to be the academics. I want to get rid of, get out of this academia to go to the industry. But then at that time, I think the pharmaceutical industry was kind of hiring freeze or cut the jobs.

So, and then this opportunity ends up to be the best opportunity at that moment. But then once I take this job, I take seriously, I think, work very hard. And then I began to enjoy more and more.

So I feel, oh, maybe even though this may not what I arranged the plan, but this happened to be the good fit for me.

Kathrine

So I guess that's where the destiny part comes in then. So next, as director of the BMCMP graduate program, what do you think students should understand about graduate school and scientific training?

Professor Huang

So for the graduate school, one thing I just realized many students don't know, if you decide to go to the PhD program in the United States, I think we're very lucky. You are getting the training and then you do the experiment, you also get paid. So you don't need to pay the tuition.

You actually, not only you don't pay the tuition, you'll get some stipend to help you to live a reasonable life. And then you don't, you can really focus on the research. For the graduate student study, so it's very different.

Of course, for master's students, that's most of the time is a self-funded. So only for the PhD. For the graduate student study, it's very different from other graduate student study or the high school studies.

For the undergraduate study or the high school study, you're learning the things that has already been discovered. So you're learning the knowledge and building your foundation. For the PhD study, there are many things we don't know.

It's unexplored. We're pushing the boundary of the knowledge. So that, which means not many things will work, will really get you the result you expect.

It needs a lot of resilience. You have to be able to embrace the results, whether it's negative or positive. Then you'll be able to learn from the failed experiments.

Sometimes maybe fail the experiment may not be bad. It's kind of redirect to a new direction. So I think that's the major difference.

You have to be able to independent thinking. So the coursework you did before or the coursework you did at the beginning of the PhD study is really just to build your foundation. But those knowledge may not exactly the knowledge that you need, how to say, I should not say, may not be exactly the same knowledge for your research.

It just, you need to apply this knowledge to do something, learn something new. How do you say, you guys learn the chemistry, right? So, or the math, when you guys learn in course, and then when you take the exam, it's never the same question, but you learn basic, right?

So you have to apply those things to address new problem set.

Kathrine

So next I want to ask, what misconceptions do people frequently have about medicinal chemistry, pharmacy, or drug discovery?

Professor Huang

So I think maybe one of the major misconceptions is people probably often think scientists have a certain aha moments. In reality, progress, as I just mentioned, is mainly come from the small incremental steps and a lot of failed experiments. You have to be able to learn from those experiments.

You have to logical thinking why for each step and pay attention to details, understand the clear goal. Another misconception is the drug discovery itself. Maybe people think the drug discovery is fast.

It's a single discovery in the news, maybe make, oh, they have the blockbuster drugs. It's not maybe 10% or 5% chance those drugs come to the blockbuster. The reason is it leads, average wise, it's probably 10 years.

I think 2007, the estimate is 1 billion cost, 10 years to discover the new drug. Right now it's the inflation, so probably the cost will be higher. And it also is a multidisciplinary process.

Kathrine

Mm-hmm.

Professor Huang

My favorite story probably is the game changer for the modern drug discovery is the Gleevec, which is a drug that treat a CML chronic melanoma leukemia. So this one, from the starting point to the way in, this one actually was discovered in Philadelphia, the fusion protein that is directly related to this disease. Over 95% of patients have this kind of, we call the BCR-ABL protein.

And then by understanding that, then designing inhibitor, then you have to do the cellular study, animal study, eventually go to the clinical trial. We're all different, so the successful clinical trial is still the big bottleneck for the drug discovery because everyone is different. We have different genetic background.

We may have a different response. And so right now the directions go to more precision on drug discovery. So bottom line is it take advantage to discover a drug.

That's why the new drug cost is high because it not only cost for one drug, essentially it's the cost maybe for many drugs that eventually go to market. Then you have to have funding to support the continuous drug discovery for the new drug to address the new problem. Also, it's a lot of the creativity, preservance, also the troubleshooting skills to really like even interpret the data and need some real imagination to really understand everything is different.

There's no recipe to a drug discovery.

Kathrine

So finally, what is one step a high school student could take this month to explore medicinal chemistry, chemical biology, or drug discovery?

Professor Huang

I think you set up a good example if you're doing this interview. You kind of understand the process. I think probably there are two potential options.

One is there are some, how do you say, the chemical engineering news, discovery. If you're really interested in some drug discovery, there are some drug discovery story. Like what I mentioned, Gleevec, insulin, those are also started from the academia eventually and go to the market.

Another option is like you are doing now is you can reach out to the professor or scientist either in the industry or in the university. Maybe either if it's close by, you can ask if you can visit their labs, maybe for a half-day shadow what they're doing. Or you can set up like what you're doing now is interview and understand the more inside news.

I think those are maybe some scientific camp in the university. So right now with the internet, there are many available information for the student to get. But one thing I really want to point out is so different, like say our department, we have nearly 30 faculty is under the same department.

And eventually all the goal is we want to discover new drug. But each lab, we're taking a different strategy. We're working in a different area.

So if you're going to PhD, is this particular lab research will be more important than whether it's the department or the other department.

Kathrine

So that's a great place to end. Thank you so much for sharing your work and your advice with me. I really appreciate your time.

And I think students will learn a lot from hearing your perspective.

Professor Huang

You're very welcome. It's nice to talk with you.