Terry Watnick

Member since 2 years ago

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6 ideas posted

1 comment 6 votes

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Years in Research or Practice?:

10-20

What is your primary focus?:

Other

Degree:

M. D.

Affilliation:

Johns Hopkins School of Medicine

Do you do research?:

Yes

Do you see patients?:

Yes

Are you a lay person?:

No

Work Zip Code:

21205

Terry Watnick is a member of:

• KIDNEY RESEARCH NATIONAL DIALOGUE-PHASE I

Activity Stream

Ideas contributed by Terry Watnick

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  PKD »

  Proliferation of Pkd1 cleavage products

  There have been a number of cleavage products described for PKD1. Autoproteolytic cleavage at the GPS site yields two fragments and a knock in mouse model harboring a mutated GPS site develops cystic kidney disease. There have been at least 3 additional C-terminal cleavage fragments reported in the literature. Many of the studies were performed using recombinant over expression systems. The occurrence/relevance of these ...more »

  There have been a number of cleavage products described for PKD1. Autoproteolytic cleavage at the GPS site yields two fragments and a knock in mouse model harboring a mutated GPS site develops cystic kidney disease. There have been at least 3 additional C-terminal cleavage fragments reported in the literature. Many of the studies were performed using recombinant over expression systems. The occurrence/relevance of these Pkd1-derived products in vivo is unknown. Rigorous studies are needed to better define the biologic significance of these observations.

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  Submitted by Terry Watnick 2 years ago

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  14 votes

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  PKD »

  Cilia and cyst formation: guilt by association

  A convergence of data suggests that cilia are important in the pathogenesis of PKD. Despite intense investigation, the precise nature of this relationship remains unclear. It has been suggested that the the PKD1/PKD2 receptor channel complex acts as a flow sensor on renal epithelial cells. When this complex is inactivated (for any reason), cyst formation occurs. However, disruption of TRPV4 in MDCK cells results in ...more »

  A convergence of data suggests that cilia are important in the pathogenesis of PKD. Despite intense investigation, the precise nature of this relationship remains unclear. It has been suggested that the the PKD1/PKD2 receptor channel complex acts as a flow sensor on renal epithelial cells. When this complex is inactivated (for any reason), cyst formation occurs. However, disruption of TRPV4 in MDCK cells results in absence of flow mediated signaling yet TRPV4 Knock out mice do not develop cysts. We need to understand the precise relationship of cilia to cystogenesis.

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  5 comments for Idea: Cilia and cyst formation: guilt by association

  Submitted by Terry Watnick 2 years ago

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  5 votes

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  PKD »

  Time course of cyst formation

  In conditional mouse models of cystic disease, renal inactivation of PKD genes after P12-14 results in delayed development of cystic disease. What is going on in the kidney during that period of time? Does the same happen in human PKD, is gene inactivation occurring continuously?

  1 comment for Idea: Time course of cyst formation

  Submitted by Terry Watnick 2 years ago

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  14 votes

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  TRAINING »

  Do we need a new model for Training Physican Scientists?

  There are fewer and fewer nephrology trainees opting for a career in laboratory based kidney research. In our own training program the vast majority of renal fellows who want an academic career pursue training in clinical science. There are many reasons for this including (but not limited to) an extended training period in a field in which they may have little prior experience, the perceived uncertainty of maintaining ...more »

  There are fewer and fewer nephrology trainees opting for a career in laboratory based kidney research. In our own training program the vast majority of renal fellows who want an academic career pursue training in clinical science. There are many reasons for this including (but not limited to) an extended training period in a field in which they may have little prior experience, the perceived uncertainty of maintaining adequate funding over the long haul and the difficulty inherent in "wearing many hats". Another observation is that lab based science is like a cottage industry with each investigator ultimately working independently. There is less of a role for group interactions that might provide a more supportive environment for physicians who are under a lot of pressure to obtain salary support. If the community believes that practicing M. D.s can make valuable contributions to basic research, what do we need to do to recruit, train and retain these individuals? Should all M. D.s who choose a lab based career obtain a Ph.D.? Should M. D.s who want to do basic research participate in larger cooperative groups? How are M. D.s doing in comparison to M. D./Ph.Ds and, Ph. D.s in terms of R01 grant funding?

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  12 comments for Idea: Do we need a new model for Training Physican Scientists?

  Submitted by Terry Watnick 2 years ago

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  4 votes

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  PKD »

  Proliferation in cyst growth

  It seems intuitive that there must be proliferation of cyst lining epithelia for renal cysts to expand. However, the degree to which this occurs has been debated in the recent literature. Proliferation may be more of a factor while the kidney is developing. This question has important clinical implications since many anti-proliferative therapies are being proposed to treat PKD. What experiments can be designed to ...more »

  It seems intuitive that there must be proliferation of cyst lining epithelia for renal cysts to expand. However, the degree to which this occurs has been debated in the recent literature. Proliferation may be more of a factor while the kidney is developing. This question has important clinical implications since many anti-proliferative therapies are being proposed to treat PKD. What experiments can be designed to rigorously address this issue?

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  8 comments for Idea: Proliferation in cyst growth

  Submitted by Terry Watnick 2 years ago

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  8 votes

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  PKD »

  Activation of the PKD1/PKD2 complex

  PKD1/PKD2 may function as a receptor channel complex. In over expression systems, which are frequently used in the published literature, the complex appears to be constitutively active. What activates the complex in vivo? What are the ligands for this complex?

  1 comment for Idea: Activation of the PKD1/PKD2 complex

  Submitted by Terry Watnick 2 years ago

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