Browse Ideas with tag 'pkd':

Early detection of renal cysts in ADPKD

Stage: Active

Campaign: PKD

A Proposal Autosomal dominant polycystic kidney disease (ADPKD) develops in utero and the cysts progressively enlarge but usually go undetected until the 4th or 5th decades of life. Recent evidence indicates that injury to parenchyma accompanied by irreversible fibrotic changes may begin to develop in the cystic kidneys during the first decade of life yet patients are currently being denied many years of supportive ...more »

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1 vote

Estrogens and Polycystic Liver Disease

Stage: Active

Campaign: PKD

Women have more severe polycystic liver disease than men and estrogens likely contribute to its progression. The severity of polycystic liver disease is highly variable. Genetically determined differences in estrogen metabolism and downstream signaling may account for this variability and should be investigated.

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The mouse as the PKD model organism.

Stage: Active

Campaign: PKD

The community has invested a lot of resources in developing mouse models for PKD. Yet, none of these models "really" recapitulate the human disease. One obvious solution is to try to tweak the mouse system even further. However, this "inability" may tell us something about PKD itself. Maybe the mouse is not the ideal system to study PKD and it is time to look at some other higher vertebrates.

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1 vote

What causes the "second hit"?

Stage: Active

Campaign: PKD

While the two hit hypothesis is generally accepted as one of initiation factors in the development of ADPKD, little is actually known about how the second hit happens. I think it would be worthwhile to better understand this process. While it will not "cure" patients with PKD, it may provide an angle to prevent the occurrence of the disease in people that carry one mutated allele. It may be easier to prevent the second ...more »

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2 votes

Proliferation of Pkd1 cleavage products

Stage: Active

Campaign: PKD

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 »

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3 votes

Cilia and cyst formation: guilt by association

Stage: Active

Campaign: PKD

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 »

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14 votes

Time course of cyst formation

Stage: Active

Campaign: PKD

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?

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5 votes

What are the roles of polycystin-1 and fibrocystin?

Stage: Active

Campaign: PKD

Although we have know that these molecules are the most important causes of ADPKD and ARPKD, respectively, for many years, and despite the fact that many ideas about their functions have been published, I am not convinced that we have it all figured out yet. Thinking a little more how we can reconcile the published data and considering carefully how we can find out more about their real functions would be worthwhile. ...more »

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8 votes

Big and small science

Stage: Active

Campaign: NORMAL BIOLOGY/DEVELOPMENT

Many younger investigators are drawn to big science labs where large scale GWAS, genomic, proteomic and other 'omic studies are performed. The expertize for teasing out defined physiological mechanisms is slowly but surely being lost. We need to ensure that funding is distributed in such a way that precious resources are not consumed generating mountains of data that may never be appropriately analyzed - we don't even ...more »

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15 votes

Discovery Work Flow

Stage: Active

Campaign: NORMAL BIOLOGY/DEVELOPMENT

One fundamental problem in our field is the lack of an integrated work flow to address clinical issues. For example, developmental models (zebrafish, xenopus, mouse, chicken), lack some genetic power (xenopus, chicken). Cell biology model systems utilize cells from dog, monkey, human, rat, mouse, possum, pig and are frequently used but findings seldom transfer to developmental systems or physiological systems (rat, ...more »

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3 votes

Do we need a new model for Training Physican Scientists?

Stage: Active

Campaign: TRAINING

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 »

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14 votes

Proliferation in cyst growth

Stage: Active

Campaign: PKD

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 »

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4 votes

Activation of the PKD1/PKD2 complex

Stage: Active

Campaign: PKD

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?

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8 votes

PKD and renal repair

Stage: Active

Campaign: PKD

A lot of research has been focussed on the potential of a renal stem cell. Even the identification of such a population is not a solution, even more so in some instances. Will regenerative options be the same for ciliopathies versus other dysplasias or renal disorders?

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7 votes

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