March 2011


Professor Arnim Pause and Jocelyn

BHD Researcher Interview: Professor Pause is a biochemist at McGill University in Montreal, Canada.

1. How did you get interested in BHD research?

I have been working on the function of VHL in kidney cancer for 15 years when I saw the paper from Laura Schmidt and the group at NCI in Cancer Cell about the identification of FLCN as a novel tumor suppressor gene in kidney cancer.

2. What are you currently working on?

I am working on the functional characterization of FLCN in the model organism C. elegans (worm), mammalian cells and mice. We are interested in the signalling pathway which is driven by FLCN. We also want to find out what exactly FLCN does as a protein. We found that it harbours a GTPase activity together with Ravi Nookala and Tom Blundell from Cambridge. We are now working on the process which is influenced by this activity to better understand the function of this protein. In addition, we are working on the relationship between FLCN and AMPK which is an important signalling molecule in tumour metabolism.

3. What would help current research (equipment, technique, etc.)?

Right now we perform all our worm work in the lab of our collaborator Dr. Richard Roy in another building. His lab has helped us setting up the worm project since we had no prior experience with this. However, now the three people working in this area have to travel to do the work several times a day. It would help us tremendously if we could set up a small worm working area in our laboratory. This would involve a couple of microscopes and incubators.

4. What recent developments in the field have interested you most?

I am very intrigued by the recent revival of cancer metabolism. This is an area which was studied in the 1930s by Otto Warburg and is now again at the forefront of cancer research since we have now a whole array of novel tools to study metabolism of cancer cells. The idea is that cancer cells such as BHD tumours have an altered metabolism compared to the normal counterparts in our body. Once we understand these differences we can target the tumour cells with drugs that affect metabolism. Many of these drugs are already available we just don’t know yet which combination we should use.

5. Do you have a favourite research paper?

Yes, I enjoy papers where disease genes are identified such as the one mentioned before in Cancer Cell by the groups of Laura Schmidt, Lerman, Linehan, and Zbar, where FLCN was identified. These papers are crucial for the understanding of diseases and provide an entry point for further mechanistic studies to unravel the pathway which is affected in this disease. These studies are require a lot of effort, patience and precision and are usually performed by many groups in a collaborative manner since one group alone could not perform the vast amount of work. Also, papers like this inspire scientists like myself to engage in the functional studies on these disease genes.

6. What are your short/long term goals?

In the short term we would like to position FLCN into a signalling pathway which we could target with drugs. In the long-term we would like to figure out the precise molecular mechanism of FLCN to target it specifically.

7. How do you see the field developing in the next ten years?

This field will grow rapidly in the future because it will become apparent that FLCN and BHD is just the beginning of the story. I am sure that the associated pathway is involved in many types of cancer and other metabolic diseases, which will draw more and more interest.

8. What’s your favourite book/film/music?

My favourite book is by Sir Peter Ustinov (Look out! Prejudices). It deals with the phenomenon of prejudices which we develop against other people. Prejudices are the starting point of a lot of suffering, many conflicts and disasters in this world.  My favourite music is the blues and my favourite artist is right now is Gary Moore, who unfortunately died recently way too early.

9. What did you want to be when you were younger?

I wanted to be an inventor/engineer.

10. Where do you see yourself in 10 years?

Doing what I do now.

11. What’s the best advice you’ve been given?

 Don’t make enemies, do important things yourself, and don’t trust anybody.

12. Do you have a scientific hero, dead or alive?

Dead: Charles Darwin. Alive: Nahum Sonenberg, my PhD mentor at McGill University.



BHD Personal Story: Jocelyn is from the USA.

1. When did you first get diagnosed?

July 2008.

2. What symptoms prompted the BHD diagnosis?

Two collapses on the right lung, VATs with talc on the right lung, and then researching on my own on the internet, combined with my dad and uncle’s symptoms being described on the BHD website, then presenting the information to my pulmonologist who found a way to have me tested.

3. What impact did the diagnosis have on you?

I was not surprised, I was really just looking for confirmation.  I felt vindicated as the first doctor I suggested this to brushed me off saying I might think I had 10 genetic diseases I had found on the internet.

4. Have you explained BHD to family members?


5. What implications do you think it has it had on your family?

It has explained the reason behind my dad and uncle’s lung collapses, surgeries, and my uncles’ bumps on his face. My dad had the testing done recently and was able to have it done for much cheaper by providing my results to the doctor.  Other family members have taken it in stride. It is at least an answer if any of the rest of them have collapses or any other issues associated with BHD.

6. Where did you go for more information on BHD Syndrome?

The website.

7. Do you have advice for people who are looking for a diagnosis?

Only that as far as I know right now, it could be hard to get affordable life insurance after being diagnosed.  Also, that a diagnosis doesn’t help prevent anything from happening though it does at least mean you should have yearly kidney ultrasounds. Blebs in the lungs though, as of right now cannot be stopped, so there is only the surgical option if they collapse. So do you want to know and then worry about it or are you the type to feel better for knowing? Or just wait and see if you develop a problem.

8. Has it affected you as a parent?  E.g. telling your children, starting a family, genetic counselling.

I had already had my 3 children. I am not against having more children to avoid the risk of passing BHD to them, however I don’t want to put my body through that as it might be too much strain and stress if I have a collapse during pregnancy or afterwards while nursing a baby.  If we have more children we will adopt.

We have not had genetic counselling. I have decided not to test my children right now, as it would involve a blood draw and that would be traumatic for them. I will talk to them about the risks and what a collapsed lung feels like (or did feel like for me), and let them decide as teens or adults whether to be tested. That is, assuming that they won’t have any issues of BHD presenting itself before then. I hope not. My dad’s first surgery was at age 18 and mine was at age 33.

9. Do you have tips and advice for caregivers?

This was hard on my husband. He had to take care of our kids, ages 8 months, 3 years and 5 years. Our 8 month old was not taking a bottle, so he had extra stress with feeding and comforting her on top of being the primary caregiver and worrying about me, and also packing up and bringing the kids to see me. It was more about him being the kids’ caregiver than mine. ;)  I had my aunt and grandma helping me post-op and they were great about letting me take naps and not letting me lift heavy things.

10. What are your current symptoms?

I am feeling fine now, but since my surgery I have had at least 2 small collapses on the bottom part of my lung. The talc and mechanical pleurodesis are keeping it from collapsing all the way. Both times my doctor has said for me to avoid flying and to let the air reabsorb on its own, and it has. I am still not sure when/if I should fly, or perhaps try a continental flight. We recently moved from Germany back to the states and were authorized to travel by ship to avoid possible complications from flying.  I also sometimes have what I jokingly call “lung flatulence” – this is towards the end of a collapse resorbing on it’s own.  When I breath I can hear and feel air bubbles escaping. This tells me the collapse is just about gone.  I have felt it occasionally even after having CT scans to show the collapse is resorbed, so I think that I still get small bubbles now and then…I especially notice this after a stressful day(s).

11. What treatment are you having, and have you had?

2 chest tubes, followed by 1 VATs with mechanical and talc pleurodesis. (where I was flown from Germany to DC and back afterwards…which probably led to the complications with collapse since then…combined with more blebs on the bottom part of my lung where the collapses keep recurring.) However, I had the VATs with talc before the docs knew what they were dealing with. Knowing now that it is BHD and could mean more VATs, it might have been best to do only mechanical pleurodesis according to my pulmonologist and a German lung surgeon I spoke with.

12. How did you find a doctor?

As a military spouse in Germany I had only one option, go to the pulmonologist assigned to me through the military hospital. However after my first surgery, if I had needed another one, I would have seen a German lung surgeon to avoid flying again.  Also, after surgery, I saw a different pulmonologist than the first due to a family emergency she had….hence I had slightly different advice from the second.  I appreciate the first pulmonologist and her opinion that I did not have LAM, however I am glad I had the second one who wasn’t going to send me back to DC for another surgery and took the resorbing route with my collapses post-op.

13. Do you have advice for people living with the BHD?

I only have the experiences with pneumothoraxes and bumps, fortunately no kidney cancer.  My advice is just to pay attention to how your body is feeling, don’t ignore it if you think something is wrong, but otherwise to enjoy life and stay active, exercise, etc.. Also don’t be afraid to stand up for yourself with your doctors – they are learning about BHD as much as you are. And make sure to get yearly kidney ultrasounds.  Also, in my experience, collapses can be hard to see on an x-ray. My pulmonologist has insisted that I have CT scans to get a more accurate view of what is going on in my lungs.

14. What has been your experience of the healthcare system and healthcare professionals?

I am in the military healthcare system as my husband is active duty Air Force. It has been a roller coaster experience so far, but we are fortunate not to have any co-pays or deductibles. My first CT scan was after my 2nd lung collapse (and chest tube) which happened within a few days of each other.  I had been saying, since my first collapse, that my dad has had this. The doctors were not listening to me.  After my CT scan the surgeon came to tell me (before my husband arrived to the hospital that day) that he thought I had LAM. This was devastating news. The military was planning to move us back to the US to hopefully find treatment for me.  My family was a mess, of course, thinking I had 1-5 years to live. After 28 hours of thinking this and having social workers and chaplains visit me to ask how I was doing (I didn’t know how I was doing…they were coming in to ask every 5 minutes!), I finally had a pulmonologist come visit me to ask about my dad’s history with his lung collapses.  She said she was not ready to say that I had LAM and was pretty mad that I was being made to think that when I hadn’t had a biopsy done yet. She still wanted me to fly to the states for surgery to avoid having to send my biopsy overseas for testing. We were able to get on the phone with my dad at work (9 hour time difference) and she got to ask him some questions that I wouldn’t have known the answers to.

The adventure of flying to the states on a Mede-vac with my chest tube, husband and nursing daughter (mom and sister came just in time to babysit the older kids), was pretty dramatic for us, but I felt that I was in more experienced hands. However looking back I wish I had been given the option to stay in Germany and see a lung surgeon rather than a cardiothoracic surgeon in the states that I had to fly to, and fly home 2 weeks after surgery.

Also, the docs in DC did not think that I had LAM, however they still did not know what it was that I had when I was in surgery.  I didn’t know about the implications of using talc, other chemicals, or just mechanical pleurodesis. Had I known, and had I known that I had BHD and that that could mean more surgeries, I would have asked for only mechanical pleurodesis. Part of the reason for letting the air resorb and not do further surgery is that the talc now makes the procedure more complicated.

Then, as noted above, I ran into a surgeon at my follow up appointment back in Germany, two weeks after my surgery, who saw the lung collapse (it might have developed in the flight or might have been there already but the x-ray didn’t catch, and then grew larger in the flight.), and who brushed off my bringing up the information about BHD. He did at least send me in for a CT scan after seeing the collapse on the x-ray, and let me go visit my pulmonologist (the one who said she wasn’t ready to call it LAM), and she was the one willing to investigate the BHD possibility.

The air after that surgery resorbed after 5 months. I was approved to fly to Italy (from Germany) and had a follow up x-ray after that, and all looked fine, so we decided to fly to California a couple months later. During packing, I felt the familiar collapse feeling again. I went to the ER on a Saturday night. They did an x-ray and said they didn’t see any collapse. I explained that I was flying on Monday and needed to know whether it was safe to fly or not. They said that I was a complicated case but that they saw no reason for me to not fly.

I emailed my pulmonologist after this and he said to have a CT scan when I returned.  Sure enough when I returned, the collapse was bigger. He looked up my x-ray from the ER visit and he could see the collapse. He was not happy with the ER. He said there would be some “quality control” for that and would make this an educational opportunity for the ER radiologists.  The air from that collapse resorbed after about 3 months. It was then time to move back to the states and with the unpredictability of my lungs, we were approved to move back by ship (which took another set of headaches and red tape but at least was successful in the end).

Since we just moved I have been referred to a new pulmonologist and I am the first case of BHD she has met. I am still educating her about how my doctor handled my post-op pneumothoraxes…as of now if I have another one she would want me back in surgery and I am not convinced that is the best option, but might be inevitable at some point. I have not been able to get my medical paperwork to her yet, but have applied for the release of that so I can take it to her, and she has seen my CT scans which I have on a CD.

15. Has BHD had any health insurance implications for you?

 Not yet, but could once my husband is not active duty any more.

16. What are your thoughts for the future?

This is an interesting question for me to ponder having an answer to. Right now I am just raising my kids and homeschooling one of them.  I am not sure what I will do when they are not requiring my active parenting anymore.  I have my dad to look to who has had 3 lung surgeries already, and though I know I haven’t followed his pattern exactly, I know that whatever happens to him regarding his lungs the rest of my life I will wonder if that is going to happen to me too. In a way he has the “luck” of not knowing what will happen as this did not present itself in either of his parents.I do hope that there will be success in finding some sort of gene therapy for those with BHD to prevent the blebs from forming. In which case I would get my kids tested and start the therapy!

17. What advice would you give to someone who has just been diagnosed with BHD?

Depends on what aspect is affecting them. I don’t have experience with kidney cancer and that certainly seems more devastating than blebs in the lungs, though that presents a whole set of special circumstances as well.  It is hard to accept at first, and could mean a lifetime of visits to the hospital, but think of this as “maintenance” and know that you can still enjoy a long life.  Just be sure to educate yourself, your doc, and stand up for yourself even when the experts are telling you otherwise (ie my answers in question 14).