September 2014

Ming Yan and Mary

BHD researcher interview: Ming Yan is a PhD candidate in Professor Arnim Pause’s lab at McGill University, and a holder of Doctoral Research Award issued from The Canadian Institutes of Health Research (CIHR). His dissertation focuses on molecular signalling of FLCN and its binding partner AMPK in tumour metabolism in Birt-Hogg-Dubé Syndrome.

1. How did you get interested in BHD research?

When I started my PhD program at McGill University 2010, Professor Pause introduced me to the BHD project. I was really excited about the phenotypic variation of this syndrome and impressed by the fact FLCN interacts with FNIPs and AMP-activated protein kinase (AMPK) complex in tumour energy metabolism.

2. What are you currently working on?

I am currently working on the adipose-specific knockout of FLCN using a mouse model. As the major form of energy storage, adipose tissue provides body fuel and releases important hormones. Its disorder induced by deficient FLCN may have long-term effects on whole body energy status in BHD patients. I hope our research will lead to establishment of an important molecular signalling pathway in tumour metabolism.

3. What would help current research?

Metabolomics approaches may provide more advances in detecting hundreds of metabolites in tumour tissues and enable much better understanding of how cancer cells use glycolysis as fuel for tumour development.  This growing and powerful technology would be also useful to discover metabolic biomarkers linked to BHD patients.

In general, I think that funds are the bottle-neck for research.

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

I am fascinated of the recent published papers that partially elucidate the function and mechanism of FLCN. Those papers show that FLCN regulates autophagy by ULK1 phosphorylation, and FLCN modulates tumorigenic metabolic reprograming, also known as the Warburg effect, by the FLCN/AMPK/PGC-1/HIF pathway.

5. Do you have a favourite research paper?

My favourite BHD paper is the FLCN gene identification by Laura Schmidt’ group in Cancer Cell. This study provides us a fundamental base for further investigation on function and mechanism of this disease.

6. What are your short/long term goals?

My short term goal is to finish my PhD thesis on BHD study. My long-term goal is to continue my research on tumour metabolism in BHD syndrome, publish one or more papers. It would be great if I can figure out a defined molecular mechanism of FLCN for development of therapeutic targets.

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

With the growth of new technology, such as metabolomics, next-gen sequencing and bioinformatics, I believe we will have much better understanding of FLCN’s function and mechanism, thus providing more options for BHD patient therapeutic intervention.

Light-hearted questions:

8. What is your favourite book /  film/ music

I like reading biography, national geographic magazines. My favourite film is the Lord of the Rings. And I love Yoyo Ma’s cello music.

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

I don’t remember any specific occupation, but from a very young age, I wanted to sail out, traveling around the world.

10. Where do you see yourself in 10 years?

Hopefully, continuing to do cancer research and to hold my own lab to conduct cancer research.

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

Don’t put off for tomorrow what you can do today.

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

Alive: Dr. Nahum Sonenberg, a member of my research advisory committee at McGill University.


BHD personal story: Mary is from the US and was diagnosed in 2005.

1. When did you first get diagnosed?

I was officially diagnosed with BHD syndrome in spring of 2005.  I had contacted the urology dept. at NIH and asked to be tested after researching it on the internet.

2. What symptoms prompted the BHD diagnosis?

I had had years of spontaneous pneumothoraces,  starting as I recall in about 1977.  During one scary episode, I called the hospital and told them I felt like I was dying and couldn’t breathe; they diagnosed it as an anxiety attack.  I made an appointment with my doctor then, and he did not take my symptoms seriously… it was embarrassing and disappointing.  This was pre-internet, and I had difficulty researching this for myself.    Years later I had an incidental finding of a 25% collapse on a pre-employment X-ray.  (They don’t do those anymore…so much has changed in healthcare!)  Eventually I did have my left lung surgery – this was pre VATS and very difficult due to all the scarring from the persistant air outside the lung.  Years after that I had the new VATS procedure on my right lung, actually a few times, but always not totally repaired with air pockets around the mediastinum and apex.

Fast foward to 2004; I was 49 years old, and I  had an incidental finding of a lesion “very concerning” for kidney cancer on an MRI of my pelvis.  By this time, we had internet and when I found a list serve for kidney cancer,  information was there about BHD.  I had a strong family history of spontaneous pneumothorax:  there was enough other family history that I was pretty sure I would test positive.  Thanks to the information I got, mostly from Cathy Sherman, I declined the standard treatments at that time…kidney biopsy, and removal of the whole kidney.  Because BHD cancers can be bilateral, and I was, I learned it was important to save as much kidney as possible.  I fought to go outside my local urologist and get a laporoscopic partial type of surgery, which was new then.  I was diagnosed with clear cell renal cell cancer, but I had the pathology reviewed at NIH and they said, “hybrid, consistent with BHD”.

3. What impact did the diagnosis have on you?

So the diagnoses really helped me understand my symptoms, and to guide me in how I should follow up.  (I had to cancel last minute my ‘trip of a lifetime’ to the Galapagos and Amazon in 2010 due to my lung issues!)

4. Have you explained BHD to family members?

I have tried to explain BHD to other family members, because I know that kidney cancer does not normally show up until it has grown very large.  In the old days, it was known to be resistant to chemotherapy and radiation treatment.  There has been a lot of research for chemotherapy in recent years so there is more hope.

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

When an oncocytoma or similar pathology is found, as it has in my extended family, whether ocular, axillary or parotid,  I believe it is important to know of the history of BHD in our family, since this may change how the findings are managed.

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

I did a lot of reading at the time of medical journal articles, and the NIH has information on  line, and there was the “kidneyonc” listserve which was very helpful.   Things have changed since 2004, and I hope we continue to get clarification and ‘fine tuning’ of recommendations for us.  I am not as up to date on current research findings as I could be.  I continue to be watchful and thoughtful for my own health issues. I had a scare last year, because cat scans showed a lung ‘mass’ (scar tissue) was growing.  However it seems to be OK now!  Good luck and good health to all who have been bothered with BHD and it’s assaults!

Cosmetically, these bumps are getting really annoying.  Will there be an effective treatment someday?  Stay tuned to and hopefully they will share info as those awesome medical researchers publish more information!