
Chapter 04: Post-Doctoral Study at MIT and Work on Oncogenes: the neu oncogene and c-erbB2 gene
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Description
Dr. Hung observes that he was always interested in how biochemistry research could connect to human disease. He explains that key scientific discoveries were made in 1982 that made the time perfect for someone in molecular biology to begin working on disease, particularly Dr. Robert Wienberg’s work on oncogenes. Dr. Hung describes his interview with Dr. Wienberg, which took him to MIT for post-doctoral work (’84 – ’86).
He next discusses project cloning an oncogene from the neuroblastoma of the offspring of pregnant rats. Dr. Hung cloned the gene in six months.
He next talks about how this work expanded into his work on breast cancer, using the oncogene model to predict mortality. He explains that the overexpression of genes resulted in breast cancer and many other cancers.
Identifier
HumgMC_01_20140220_C04
Publication Date
2-20-2014
City
Houston, Texas
Interview Session
Mien-Chie Hung, PhD, Oral History Interview, February 20, 2014
Topics Covered
The Interview Subject's Story - The Researcher; The Researcher; Overview; Definitions, Explanations, Translations; Discovery and Success; Professional Path; On Research and Researchers; Understanding Cancer, the History of Science, Cancer Research; Formative Experiences; Discovery, Creativity and Innovation
Transcript
T.A. Rosolowski, PhD:
Well, tell me what happened after you received your Ph.D. You did a Post Doc then at MIT which did not accept you before.
Mien-Chie Hung, PhD:
Yeah. So when I finished, I was thinking about ---I was always interested in disease.
T.A. Rosolowski, PhD:
Why?
Mien-Chie Hung, PhD:
And --- I --- I’m interested in disease, life science. They are both basic science diseases. A and then, remember I started on that with snake venom, or was thinking about it. But actually when I went to the lab I was very naïve. I was proposing that, can we clone snake venom protein gene from snake gene? Well we can, but then I was very naïve. Well why would you do that in that lab. That lab is a fly lab. They don’t even have a snake. [laughter] Anyway, so anyway I just worked on fruit flies. And then, in 1982, the first human oncogene was cloned. In 1982 many, many things happened. The first human oncogene was cloned and, the first human oncogene was found to be carrying a single- point mutation different from a normal gene. The only difference between normal and cancer is one mutation. And, that particular gene was found to be --- You know before 1980 many people studied cancer, and the hospital people studied cancer but they were animal-model people and they studied animal tumors. In animal tumors, they cloned it. They identified those viruses associated with the oncogene. There are a lot of genes associate with viruses, and those are so-called virus-associated oncogenes. But those virus-associated oncogenes have not been recognized as related to human cancer because that’s a --- the gene causes cancer in chickens, in mice, in rats. B but how do you know if it’s a rat or a human cancer? You don’t know. But in 1982, the first human oncogene was cloned. A and that gene was homologous to a virus- associated gene. So meaning those --- animal modela are rarer than that, and the cancer gene carry one single point mutation --all happen in the same year. So that’s meaning cancer can cause by a mutation. A mutation can be caused by a carcinogen, rrght? Carcinogens cause cancer. It’s all you hear. So suddenly NCI that year say,s W we --remember President Nixon in early 70s, 71 ‘1 or ‘72, at the War on Cancer, right?
T.A. Rosolowski, PhD:
War on Cancer. Yep.
Mien-Chie Hung, PhD:
And I still remember at that time he came in at one point and committed 1.6 billion dollars or something. Anyway. A, and NCI in 1982 says, ithis year our knowledge in cancer is more than ten10 years --- the last ten10 years. Because you suddenlycertainly know all those virus- associated oncogenes already have human cancer. And you know carcinogen-induced mutation is rarely human cancer.
T.A. Rosolowski, PhD:
How --- What an incredibly exciting year. I mean it just exploded.
Mien-Chie Hung, PhD:
And that oldest I mentioned was --- happened in several laboratories. A and one of the major labs is Bob Weinberg’s, who__ (1:10:59.7) was my mentor at MIT. So that’s the answer to your question why I went over there.
T.A. Rosolowski, PhD:
Right.
Mien-Chie Hung, PhD:
Because I was so excited. A and remember, I was trained in chemistry. I like a structure --- organic structure, organic compounds with the protein primary sequence. A and all of a sudden hey, wait a minute minute, there’s a molecule. There’s a mutation, and this is a normal gene, and this mutation cause cancer? Holy smoke. Come on.
T.A. Rosolowski, PhD:
Right. There’s the beginning of translational research right there.
Mien-Chie Hung, PhD:
Oh Oh, I was, I’m going into that field. And at that time, they had two laboratories --- three laboratories and two of those were so-called transfection. Meaning take oncogene. Back in the old days when the gene caused cancer, you can transfer cultured into a culture. Then after you transfer a culture cells and the normal cell becomes cancer cell. There are a lot of definitions of cancer cells. At that time there are two --- three labs, but two major labs, one in Harvard – Jeffrey Cooper, and the other one in MIT – Bob Weinberg. I applied to both labs. And that --- that time the lab --- those were very popular and I was lucky that I was accepted by both of them. But I was also lucky I chose Bob Weinberg.
T.A. Rosolowski, PhD:
Why?
Mien-Chie Hung, PhD:
Because they all do transfection, but Jeffrey Cooper, he studiedy another gene, and that gene turned out to be --- not a real human oncogene. So Jeffrey Cooper later on was not recognized in the field. But --- But at that time the technology is the same --- the same. I’m not saying he’s --- you know it’s just like …
T.A. Rosolowski, PhD:
It was just the luck of it. Yeah.
Mien-Chie Hung, PhD:
Yeah. Yeah. And so --- so I was --- and of course, at that time some friend told me Bob Weinberg is probably better, and I went there. So but otherwise I was accepted by both, and I was thinking about which lab to go, and then anyway I decided to go to Bob Weinberg’s lab. And then when I go to Bob Weinberg’s lab I make the same mistake. I also learned something, too. When I interviewed with him --I don’t know why he take me but I know one of his friends was our neighbor lab the co-lab. I just visited this. [phone interruption] I forgot it.
T.A. Rosolowski, PhD:
You can add it later. That’s the advantage.
Mien-Chie Hung, PhD:
So he was in our neighboring lab. And he’s a professor in my --- my _______ right? He know I work very hard. I mean every night in the lab. There, you know, at Christmas time I’m probably in the chair. And he and Bob Weinberg were in the same lab. So at the time, of course, my advisor write a strong recommendation letter, but I believe. Oh, Michael Rashbausch. Michael Rashbausch. He’s a very well-known scientist now. He’s a member of the National________ Academy (1:14:12.9), Michael Rashbausch. He --- I believe he called Bob Wein --- Oh, Bob Weinberg called him and said, Hey there’s a guy from you’re institution, [ ] --- and then he probably tell him, This guy is work very hard. And also I have --- at that time I designed some --- a trick for cloning strategy. A annd he was very impressed. I know it because I was --- our lab and their lab had joint meetings. Then sometimes I say, H hey you can do this, this and this, and people in this lab was like, holy shit, how can he brought up two sequence?. Oh, they’ll say, oh those sequence, I spent so much time, right? B but get 0.000001. B but because I sequence so much, so I remember all those sequence. So because I remember that sequence so I --- based on that I designed a very small trick --- very small trick to allow --- it’s a special technique to allow something originally very difficult to become doable. And that --- the reason we can do that is because I have a lot of sequence knowledge. A and very people --- very few people memorize those sequence because it’s very boring. But it was him right here, so therefore when I shared with their lab I mentioned that, and people told him he was not there. And they said, O oh he’s a genius and this is great idea. How come you guys don’t tell me? Okay, so anyway.
T.A. Rosolowski, PhD:
What was the --- What was the trick?
Mien-Chie Hung, PhD:
I don’t know really how to explain that. Right now it’s very easy now. I can do it all day. [Dr. Hung draws a sketch.] This is a plasmin DNA. For cloning people say this is bacteria plasmin and this is a human gene. Okay? I want to put this piece of DNA, [in] this human gene. I’m going to put this one here. So I can replicate a human gene in bacteria so I can make whatever I want.
T.A. Rosolowski, PhD:
Okay.
Mien-Chie Hung, PhD:
For us to do that the DNA needs to use enzyme to cut it. A and this enzyme is called _______ enzyme. The person who discover it I think received a Nobel prize. A and the __________ enzyme usually had to be --- this is A enzyme and this is B enzyme. To put this piece here, you, need to have an A enzyme side and B enzyme side here so that you put it here.
T.A. Rosolowski, PhD:
So it would just like be a puzzle?
Mien-Chie Hung, PhD:
Yeah, so you can put it in.
T.A. Rosolowski, PhD:
Yep. There ya you go.
Mien-Chie Hung, PhD:
And this enzyme recognized sequence so-called protruding in like ATGC, double strand, let’s say ______ . And then you --- Double strand. aThen you know the DNA sequence of G pair to C, you know. Okay, okay. So this enzyme has this --so only when you have another enzyme identical so we can pair them. So C pair to G, G pair to C, okay? But I discovered you don’t have to be 100 match --- 100% match. You can miss one. And the reason I can design a pair ---and I know which enzyme was sequence, because I sequence all the time, right? And so --- so then you’ve missing --- you’re missing one it’s still right. So now originally this had to be A to A, B to B right? Now I can make it more flexible. A can go to maybe D, and B can go to F or something like that and of course the frequency is lower. However, for cloning you just need one.
T.A. Rosolowski, PhD:
How neat.
Mien-Chie Hung, PhD:
And also you have enzymes. And so when I say that and I can read a sequence right away. I say this sequence in back, and the other enzyme come this, so they are paired and then it makes sense. And it --- And when I proposed that my advisor said it’s not going to work because you have one missed pair. However, because there’s an enzyme, there so actually it worked.
T.A. Rosolowski, PhD:
And that’s --- that again shows the advantage of just going through the process. Yes.
Mien-Chie Hung, PhD:
Details. Yes. If I use everything kit …
T.A. Rosolowski, PhD:
Yep. You would have never discovered that.
Mien-Chie Hung, PhD:
This is not going to be important because we can sequence everything now. B but at that time there’s no trick.
T.A. Rosolowski, PhD:
Now is --- was it significant? I mean did --- did it give you interesting information to know that they didn’t have to match?
Mien-Chie Hung, PhD:
Oh no, no. Because this becomes very powerful. Because before --- back to the old days, there’s no _______ . But you have --- for you to clone this, this is the only choice, period.
T.A. Rosolowski, PhD:
Right, right.
Mien-Chie Hung, PhD:
But now I make it more flexible, so it [doesn’t]don’t have to be that way. You have some --- not --- not random but, yeah, this is not the only option. I can give you another five options.
T.A. Rosolowski, PhD:
But did you learn something about the chemistry or the biochemistry to know that they didn’t have to match? I mean was it not just convenient, but did it give you more inf – more knowledge?
Mien-Chie Hung, PhD:
No. No. It just --- It’s just a sixth sense. See --- Okay, now for DNA and DNA to pair, you have to be this one, this one, this one. A and then I asked, H how about if we have one missed pair? And then four out of --- three out of four pair? It should be better than no pair, right? And then keeping in mind this required an enzyme. The enzyme is beautiful. The enzyme can make it frequency --- increase much higher. A annd plus we are talking about cloning. Cloning I don’t need every one of them to come out to what I want. I only need one out of 100 to come --- 1 out of 100 and that is it. There’s no other way to screen it. I pull out that one, then the beauty of cloning is once I have that one I have everything.
T.A. Rosolowski, PhD:
You have everything. Right. Yeah.
Mien-Chie Hung, PhD:
And so he was very impressed on this one and Michael --he still talks about it.
T.A. Rosolowski, PhD:
That’s cool. Yeah.
Mien-Chie Hung, PhD:
And --- And actually when I came here as assistant professor, Jeff Rosen in Baylor, he’s still there. One time we talked about collaboration. We talked about cloning strategies and he said, Ooh, there was a paper you know in the university of all this, [about] this and this, and I said, O oh, that was my paper. Because this [became abecome] powerful thing and at that time --it’s no longer –[it’s]gone on t ancient history now. So anyway. So Bob Weinberg obviously called Michael Rashbausch, and Michael give me a lot of good recommendations so Bob took me in and --- and when I went into his lab the first thing I was --- because he’s in news all the time --- in --- in 1982 he was even in ________ (1:20:07.7)a picture of Continental. His picture was in Continental Airplane. So he was very hot at that time. But he cloned human oncogene, identified mutation, and --- oh, at that time people thought he was going to get the Nobel prizePrize. He didn’t get it, but anyway. And when I went into his lab for the first time, I didn’t prepare that [anything]. He asked me, he said, W what do you want to do? I thought I come here and he was going to tell [me] what I’m supposed to do, right? And when I was in BrandiceBrandeis in the last year I was involved in the project to put the gene into the fly. Gene into the fly and that --- that --- at that time it was brand new. Right now it’s doing all the time now. So I said, M maybe I’ll put oncogene to fly. A and he said, T then what? I said, W well, fly develop cancer. He said, O okay then fly develop cancer, then what? Put anymore models and publish it. And he said --- he said well --- again, I agreed with him just like similar to when I talked to my Ph.D. advisor I want to do snake cloning --because the lab doesn’t do that. Weinberg’s lab is doing human oncogene, mouse oncogene, why doing fly study? He doesn’t even have fly in the lab? Right? So I was not thinking. So anyway he --- And it doesn’t mean that you put oncogene and develop fly cancer is wrong. People did that later on, and it turned out be a model. But you should not do it in his lab. His lab is for some other more interesting project to do. So anyway. So in his lab then I --- And his lab is very different from Pieter’s lab. His lab is very hot, about 18 or 20 people and everybody is very hot and then they all popular in the tPop journal and work very hard and then everybody there _________ and that the culture was very different from Peter’s lab. Peter’s lab everybody was so friendly. But in our lab he said, T talk to people. There was one --- I talked to this woman. They are all very nice and they all talk to you, but everybody is the same pretty much say, D don’t touch.
T.A. Rosolowski, PhD:
Right. Reserved. Not sharing. Yeah.
Mien-Chie Hung, PhD:
Don’t touch. And at that time in their lab ,they had a lot of hot labs. They had --- They had paper in Nature ______ (1:22:39.5) all the time, and it was all very hot. A and I really admired that a and so I --- They have one interesting project, which they called P185. The P185 is a very interesting animal model, and some guy, a pPost dDoc fFellow before me, tried to clone that P185 gene for two years with no success.
T.A. Rosolowski, PhD:
What did the gene do? What does it?
Mien-Chie Hung, PhD:
Let me --- Let me explain it to you.
T.A. Rosolowski, PhD:
Oh, I’m sorry.
Mien-Chie Hung, PhD:
That is from a German group. That German group has studied a very interesting chemical carcinogen. Aand put it in the pregnant rat. Then after that the offspring about 80% all developed brain tumor. Well ,that’s --- that give you a reason. So remember we said, P prregnant women don’t smoke, because it’s going to affect your baby! A and that’s one of the good example. And so they developed new brain tumor, so-called neuroblastoma or glioblastoma, okay? And they developed the cell line from that tumor. And Weinberg’s lab at that time is very hot, as I mentioned doing those transfections, very hot. To be able to clone an oncogene from a tumor. E, either from human tumor --- the first one human tumor or from mouse tumor or whatever. So they are interested to clone that neuroblastoma gene. The gene cloned because they say, T this is from pregnant rat. Y you give carcinogen, and then offspring developed tumor --- brain tumor and then brain tumor developed culture cell line and this culture cell line is a tumor. So there must be an oncogene there, so they want to clone it, and there was a pPost dDoc fFellow who tried to do it. But that pPost dDoc fFellow --he’s very smart, bbut then he --- he’s not a molecular biologist. He’s a protein chemist, so he didn’t really clone it. B but I was trained as a cloning person in drosophila. S, so end up --and also, that --- that --- that particular tumor cell line --- before me there were a couple students and pPost dDoc fFellows who tried to identify what chain actually caused the oncogene and they have --- to make a long story short --- they have --- they take this tumor cell to develop antibody, to see whether it is something abnormal. If only something abnormal and the antibody detect a protein size 185K --- 185,000 ____ so you did it for ________ molecular weight. So because this protein it just is a human tumor --not in the tumor cell, but not introduced into the body, so tumor cell has a specific protein. So they call it the P185_______ (1:25:24.3). This P185 is the cause of the cancer so they want to clone it. But --couple people work on two or three years but didn’t clone it. And I couldn’t find athe project. And this is very difficult project and nobody want to do it. And this part is what I want you to know. My weight at that time was 185 pounds. My weight is 185 pounds. And that protein was P185. So I said sh --- in Chinese has those kind of numbers.
T.A. Rosolowski, PhD:
The numerology. Yeah.
Mien-Chie Hung, PhD:
And also I’m good at cloning, so I decide to clone that gene. But people in the lab told me, Don’t do it because another person already spent two years there. But the thing is that the background is different. So I picked that project. So in half a year --- half a year I clone it.
T.A. Rosolowski, PhD:
Half a year?
Mien-Chie Hung, PhD:
Half --- Yeah. Half a year. It’s a little difficult, but if you know how and then --- and that was for neuroblastoma and glioblastoma. So we cloned new neu oncogene, N-E-U. But in that year --- I went into his lab in 1984, January. I probably cloned it in the summertime but in September that --in Boston, he has a one symposium, he talked about it. At that time we had not published yet, so he talked about [the] new neu oncogene, and the news came out and said new oncogene, N-E-W because of new, but what we meant is that neuroblastoma newneu. But it --- actually the news reporter thought it was new oncogene, n-e-w, not a new neu oncogene, you know.
T.A. Rosolowski, PhD:
So tell me how you clo --- how you did clone it you know since you brought a different background.
Mien-Chie Hung, PhD:
So remember I told you library.
T.A. Rosolowski, PhD:
Mmhmm.
Mien-Chie Hung, PhD:
(1:27:3.6) Okay. The first thing I had to make a genome library from that tumor cell. That tumor cell --- has -- that oncogene there, right? So I had to make a library. So make all the gene piece by piece, right? So I have a library. The library can be --- The library can be plasmid, can be cosmid, can be virus, can be many things. So at that time I used the cosmid --- the cosmid because the cosmid can carry. My advisor used the plasmid. Plasmid can carry only 5-10 KB kilo______ base pair[s] but cosmid has been modified and can carry 40 kilobase pair[s] ______ .
T.A. Rosolowski, PhD:
Now what is cosmid exactly?
Mien-Chie Hung, PhD:
Cosmid is a modified --- it’s a modified factor of DNA --- a modified factor from the bacteria plasmid. Are you familiar with bacteria plasmid?
T.A. Rosolowski, PhD:
Not really, no.
Mien-Chie Hung, PhD:
Okay. Bacteria has a genome. But bacteria has also those extra chromosomes, very small, and those extra chromosomes in bacteria can make multiple copies, so that’s why we can clone the gene and make a lot of DNA. And those are --- And those plasmin are small genome. It’s different from your genome. It’s extra chromo --- It’s not your chromosome. It’s extra. The plasmin size is very small, and I told you the first sequence in _______ . It’s bacteria plasmin PVR322 and --- but they don’t people modify in order to allow the capacity to carry more because plasmin only can carry a few kilobase pair. How about your gene is 20 kilobase pair. We will never be able to clone a functional gene, right? So now people just modify it become that plasmid can carry maximum 40 kilobase pair from 4 kb to 40 kbp. That would be different. And so that they call cosmid.
T.A. Rosolowski, PhD:
Oh okay. The modified --- Yep. The modified version.
Mien-Chie Hung, PhD:
The modified. And I was lucky because that functional gene, it’s just 33 kilobase pair. So if I used plasmid like bank, it’s not going to work. So I used cosmid and make it the library from the --- that cell which carried that oncogene --but the thing is we don’t know which one. A annd we are thinking about ways to fish it out. And at that time –we’re making a long story now. At that time the --- there’s --- Yyou know EG receptor? Okay. The --- Mendelsohn, Okay. EG receptor called in by a gene called ErbB gene_______ (1:29:48.6), and --- and at that time, genetics in English group had just cloned the gene. And it’s --- it’s originally associated with virus called vErb gene --- remember I told you those people study animal virus and they carry oncogene right? V stem for virus --- So ______ stem from that particular gene pool, and they told me that ErbB gene _______ (1:30:11.8) was found to be human EG receptor. And we are suspecting this P185 [would be] a very homologous to EG receptor. There’s some _______ (1:30:39.4indirect evidence) so we end up use V- ErbB _______ (1:30:31.9) as a DNA probe. Keep in mind V- ErbB_______ (1:30:36.0) is from a virus. It’s a chicken virus. Yeah, it’s an animal virus. It’s not human. It carries the oncogene so --- but all the oncogene, they are homologies so you can use the hybridization technique. So we used it to hybridize it --- the library which I made from that mouse tumor, right? A and then to see which one hybridize with that. And then I freeze that. And then after I clone it turn out to be 33 kilobase pair. One piece function gene with the biology I kept. And the biology I kept it had to be done by transfection. In other words I transferred into a normal cell and of that normal cell I found cancer cell.
T.A. Rosolowski, PhD:
Cancer cell. Wow.
Mien-Chie Hung, PhD:
Yeah, so we have cancer twice. So now I know I cloned that gene. And so --- in that gene they don’t --- another student who uh took that project to identify what caused this gene [to be] different from a normal gene and to --- now they see what kind it is. One single point mutation.
T.A. Rosolowski, PhD:
One single point mutation.
Mien-Chie Hung, PhD:
Yeah, just like the first human oncogene.
T.A. Rosolowski, PhD:
In the first human oncogene.
Mien-Chie Hung, PhD:
The first human oncogene was in 1982. Our paper was in 1986. And so that --- this is rat --- is a animal neuroblastoma right and then it’s single point mutated. And the funny thing is when I came here the first time, you know Arthur Yungoung [Oral History Interview] here? He has collaboration with me because he work in neuroblastoma. A and this is neuroblastoma so we were actually interested and we had some collaboration at that time. We tried to study whether this gene is available in human tumor. Turned out to be that’s not the case. And you know why? Interesting. In the animal case, you require one single point mutation in DNA to change the amino acid from _________ (1:32:34.5) inglucamine into glycine. One single point mutation change that specific amino acid. You know the animals can change, right? But do you still remember since we started biochemistry there’s a wobble effect? I.e. genome _________ recognized one amino acid. Remember that?
T.A. Rosolowski, PhD:
No. I didn’t actually study biochemistry, but yeah.
Mien-Chie Hung, PhD:
Okay. So --- Okay. The _______ ATGC three of them recognized one sequence. However, there are some of them co-op will say first one and second are different. The third one it can be A, B, C or A, B, D, or A, B, E. They all recognize the same sequence.
T.A. Rosolowski, PhD:
Oh, okay.
Mien-Chie Hung, PhD:
They all recognize the same sequence. So in this particular case, in the rat P185 gene, one single point mutation changed [the] amino acid. B but in human case we require two. So --- And once you require two mutations, the frequencies become very low. So the gene which I was involved cloning --called this P185 or called neu oncogene-- turned out to be --- in human it’s a human EGF receptor homologue ________ (1:33:41.9) 2 so it’s called HER2.
T.A. Rosolowski, PhD:
Oh that’s where the HER2 gene. Okay.
Mien-Chie Hung, PhD:
HER2 stands for human EGF receptor #2 and you sometimes also see people call it erbB-2 because erbB is that virus-associated compound. ErbB is really erbB and then homologous ______ (1:34:02.7) EGF receptor. And then HER2 is human EGF receptor #2. A and neu come from neuroblastoma. That gene was causing neuroblastoma in rat. So that’s why in the literature you see HER2/neu or HER2/erbB-2?. These are all the same gene. That’s where it comes from.
T.A. Rosolowski, PhD:
Huh. Okay.
Mien-Chie Hung, PhD:
But in the human case we don’t see that identical mutation because of that --- two change --- the same aminos change and require two mutation and that frequency is very low. And that HER2/neu in human cancer turned out to be involved [in] breast cancer, ovarian cancer, pancreatic cancer. A annd these kind of cancer --and they cause cancer not by mutation but my by ________ by large scale production. Extra mutation make it 1 equivalent to 100 because it can still activate it, but since they aren’t cause by mutation, they’re caused by overexpression or overimplication.
T.A. Rosolowski, PhD:
Now, okay because I mean we were --- when I was reading about your work on tyrosine kinase …
Mien-Chie Hung, PhD:
Yesah. Yeah. Tyrosine kinase.
T.A. Rosolowski, PhD:
Right. Um I read that that really --- you’re --- you’re talking about this paradigm shift. That everybody had thought about oncogenes as being kind of the ground zero, but you were actually discovering that there was actually an understanding of the way the receptors worked and not --- am I --- am I getting this correct? There was like a shift in emphasis.
Mien-Chie Hung, PhD:
I think this maybe the next one.
T.A. Rosolowski, PhD:
Okay. Well, I mean, I’m just trying to make the connection with um…
Mien-Chie Hung, PhD:
No. This is different one.
T.A. Rosolowski, PhD:
Okay. Okay.
Mien-Chie Hung, PhD:
This --- This is later on.
T.A. Rosolowski, PhD:
Well, oh good. Well let’s --- let’s --- let’s continue to tell your story then. Yeah.
Mien-Chie Hung, PhD:
Okay so --- so EGF receptor as you know --- EGF receptor is the receptor of cell service protein and HER2 is also cell service as a receptor.
T.A. Rosolowski, PhD:
They’re receptors. Okay.
Mien-Chie Hung, PhD:
And receptors meaning they were exposed outside of cell and also inside of cell. They --- They are responsible for communication outside of cell and inside of cell. Outside of cell you have something come in, and you try to pick up. Say --- So say this is a cell. Receptor like that that, but this one is outside. Something come in then they transition here and that’s usually on the inside from the receptor. Okay and EGF receptor is a portal type of receptor. HER2 is his brother, and HER2 also present turn out to be cause breast cancer. That’s why I study a lot of breast cancer --breast cancer/ovarian cancer. And then EGF receptor similar. So up to now I’m still working on these two molecules, and these two molecules turn out to be overexpression or mutation or cause human cancer. And in the case of brain tumor, turned out to be EGF receptor has a lot of mutation. All this family, all these receptor and tyrosine kinase, they do something similar. In the rat neuroblastoma, was erbB-2 mutation. In human brain tumor, turned out to be EGF receptor frequently mutating.
T.A. Rosolowski, PhD:
So it’s like you discovered this kind of central mechanism and then it was following the implications of that in all these different directions.
Mien-Chie Hung, PhD:
Yeah, and then not only me because we --- we got many people involved in this work right? So --- And then I was part of --- Well I was responsible for cloning rat genome in neu oncogene, but later on --because the gene is too big, so it’s really heavy. It’s difficult to handle, so there’s another shorter version called CDNA. It’s complimentary DNA. And then Cory Buckman is an honor student in Michael’s lab, and I collaborate with her so she was responsible for cloning the CDNA. And CDNA turned out be more usable because it’s smaller. It’s _________ (1:37:44.6)5 kilobase pair. So 5kb_________ (1:37:47.5) and 7 kilobase pair. Five kb _______ (1:37:50.3) is smaller and easier to handle. So now we all use the CDNA version. So that was where --- So when I was in the lab, I was primarily responsible
Recommended Citation
Hung, Mien-Chie PhD and Rosolowski, Tacey A. PhD, "Chapter 04: Post-Doctoral Study at MIT and Work on Oncogenes: the neu oncogene and c-erbB2 gene" (2014). Interview Chapters. 1156.
https://openworks.mdanderson.org/mchv_interviewchapters/1156
Conditions Governing Access
Open
