September 2013

Angela Pacitto and Anna

BHD Researcher Interview: Angela Pacitto is a PhD student in Professor Sir Tom Blundell’s lab at the University of Cambridge, and was part of the team that published the structure of Folliculin’s C-terminal domain in 2012. She is using structural studies and X-ray crystallography to determine the function of Lst7, the yeast orthologue of Folliculin.

1. How did you get interested in BHD research?
I was working in industry, and was keen to come back to academia to do a PhD. I wanted to work on a project that I was passionate about, in a lab where I could learn new things. When I saw the folliculin project advertised in Tom Blundell’s lab, I was really excited because the project is of personal relevance to me, having a family history of kidney cancer, and also I was enthusiastic to learn about X-ray crystallography. Fortunately I was selected, and so I have been working on the structural aspects of folliculin/fnip for 2.5 years.

2. What are you currently working on?
I am currently working on the yeast orthologue of folliculin, Lst7. I am pursuing structural studies using X-ray crystallography and also using an S.cerevisiae system to do functional experiments. I am using a proteomics approach to look at the Lst7 interactome in collaboration with Dr. Svetlana Dokudovskaya at the IGR in Paris, and just about to start some genetic experiments to try to understand the relationship of LST7 with other genes. I hope by combining these approaches I can work towards understanding the function of the protein at the molecular level.

3. What would help current research (equipment, technique etc.)?
An antibody for Lst7 would be pretty useful for me!

4. What recent developments in the field have interested you most?
The two recent bioinformatics papers by Zhang et al. and Levine et al., which showed that the fnip proteins are divergent DENN domain containing proteins, were extremely informative. It is very intriguing that the fnip proteins likely have the same fold as folliculin, albeit with large insertions within the globular regions. So with the folliculin/fnip complex what we have is a complex with two Longin/DENN domains – which as far as I’m aware is quite unique and must be important for the function.

5. Do you have a favourite research paper?
In the BHD field, the Nickerson et al paper that reported the discovery of the FLCN gene is really what kicked everything off, so of course this is a landmark paper. Also given that I am working on Lst7 at the moment, I should mention Roberg et al. 1997 where the LST7 gene was first identified due to its synthetic lethality with SEC13.

6. What are your short/long-term goals?
I have one broad goal, which is to finish my PhD with a good thesis and hopefully one or two papers that are able to add a little piece to the folliculin puzzle.

7. How do you see the field developing in the next ten years?
Although it is now more than 10 years since the FLCN gene was identified, we still are not exactly sure what folliculin is doing, and why its loss leads to disease. So hopefully the field will continue to attract talented scientists who can help work this out. Once we have placed folliculin into a signalling pathway, it will be much easier to identify druggable targets that could be used for developing a treatment for BHD syndrome. So I hope this is possible in the not too distant future.

8. What’s your favourite book/film/music?
It’s always difficult to pick just one, but one of my favourites is Pride and Prejudice by Jane Austen. My favourite films are Before Sunrise and Before Sunset and my favourite band is The Yeah Yeah Yeahs.

9. What did you want to be when you were younger?
When I was very young, I wanted to be an actress, then a doctor. Then I realised that I liked the nitty gritty details of basic science, so I studied biochemistry and subsequently pursued research.

10. Where do you see yourself in ten years?
It’s difficult to see past the end of my PhD at the moment, but hopefully still in science, enjoying what I do.

11. What’s the best advice you’ve been given?
‘Think before you speak. Read before you think’ – I read that quote somewhere and I think it’s quite a good one.

12. Do you have a scientific hero, dead or alive?
My PhD supervisor Tom Blundell, is a wonderful mentor, and he has made an enormous contribution to science in general.


BHD Personal Story: Anna is from the UK and was diagnosed with BHD in 2012.

1. When and how did you first get diagnosed?

I was officially diagnosed last year through genetic testing, after my father had been referred by a doctor who knew of BHD, but wasn’t working in an area he could help with it. I went to Dad’s appointment with the geneticist, as we knew that if Dad had it, I did too due to us both having the skin condition that goes with it.

2. What symptoms prompted the BHD diagnosis?

I have always known about fibrofolliculomas, as my Dad has had them longer than I have known him. I found my first fibro lump at the age of 13, and knew what it was immediately. Dad has also had 2 separate Pneumothoraces in the past, and I was diagnosed visually with the same skin condition 10 years ago. We weren’t officially diagnosed until Dad was sent for a colonoscopy for something totally unrelated, and the Dr recognised his skin condition, prompting a referral from our GP.

3. What impact did the diagnosis have on you?

Initially I was very worried. What would it mean for my future? I am concerned about how it will affect any children I might have (I am currently childless), and even if it doesn’t pass to them, will I be here to see them grow up? I still think of these things, but its not a constant worry. When it happens, or I have to make a decision, I’ll think about it more.

4. Have you explained BHD to family members?

Only to my partner really. Dad has it too, and Mum always comes to our appointments with us, There is no one else in the family who could have it as I only have half-brothers from my Mum’s first marriage, so it doesn’t really affect anyone else directly.

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

Its explained why dad suffered from 2 collapsed lungs, and made me wonder if I should even risk having a family. It’s something my partner and I need to think about seriously when planning our family

6. Where did you go for more information on BHD syndrome? has really been my only source of information outside of the genetic consultant, there is so little information on the web, its difficult to find anything that’s not on there.

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

Try not to worry. It’s difficult, but worrying won’t change your diagnosis, it is what it is. If you have BHD, then it’s good that you know, as you can then continue to be monitored for problems that might otherwise go unnoticed. A diagnosis IS a good thing.

8. If you have children, has BHD affected you as a parent? E.g. telling your children, starting a family, genetic counselling.

We are thinking very carefully about whether we want to have a family now, had I already had children before diagnosis, it would have been an easier choice to have another/more, but having none, makes it harder for me. In the UK, they won’t test for BHD until a child is older, as they believe that it won’t affect them til adulthood, so that’s a big consideration. Genetic counselling isn’t freely available here for syndromes like this (not directly life threatening), so if we wanted that, we’d have to pay for it.

9. Do you have tips and advice for caregivers?

Don’t be afraid to admit you haven’t heard of BHD! We know it’s rare, we probably know more than you do- you can’t know everything about all the rare diseases and syndromes, and that’s ok. We can point you towards the right places to find out about it, so ask!

10. What are your current symptoms?

Currently I have lots of the little visible lumps all over my body, I have 2 blebs in my left lung, and a 9mm cyst on my left kidney.

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

No treatment currently.

12. How did you find a doctor?

My dad was referred by our GP, and I was able to become his patient too just by going along to the appointment due to the familial link. The NHS works entirely on referrals, so the only way to see a doctor outside of a GP here is to be referred by your GP.

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

I have recently been refused NHS treatment to remove some of the lumps from my face, and despite having pain in my chest and kidney areas, I am told my blebs and cyst are too small to be causing the problems. I have pushed for yearly scans though, which has been accepted over the 3 yearly repeat cycle they wanted to follow, so that’s something.

14. What are your thoughts for the future?

I’m a generally positive person. I’d far rather go forward armed with all the facts, and knowing I have BHD and everything that comes with it is part of that. I won’t allow it to stop me doing anything I really want to do, There are just a few extra risks to bear in mind, that’s all.

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

Read all you can about it, and if you can, talk to other with the condition. Also, remember nothing has changed but your knowledge-you always had BHD, you just didn’t know it. Knowing is a good thing.