U.S. Department of Health and Human Services
ApoL1_06-2015_910x220.png

ApoL1 and Kidney Disease Conference

6/2/2015 8:30 AM
6/3/2015 3:30 PM
No
No
​​For questions concerning program content, contact:

Rebekah S. Rasooly, Ph.D. 
KUH/NIDDK/NIH
Two Democracy Plaza 
6707 Democracy Blvd., MSC 5458 
Bethesda, MD 20892-5458
Phone: (301) 594-6007
Fax: (301) 480-3510; 

For questions concerning meeting logistics, contact:

John Hare, M.S., CMP, CGMP
The Scientific Consulting Group, Inc. 
656 Quince Orchard Road, Suite 210 
Gaithersburg, MD  20878 
Phone: (301) 670-4990 
Fax: (301) 670-3815 
Hyattsville
 
College Park Marriott Hotel & Conference Center

Event Details

Event Details
ApoL1 susceptibility alleles, which are found primarily in African-Americans, are arguably the most important discovery about the pathogenesis of Chronic Kidney Disease over the past 5 years, and among the only known genetic factors contributing to the well-appreciated health disparities in kidney diseases. These variants may explain 70 percent of the excess focal segmental glomerulosclerosis, HIV-associated nephropathy, and hypertensive kidney disease in African Americans.

This conference/workshop will attempt to develop new ideas regarding and pathways to determining how risk alleles lead to disease susceptibility, what kidney and cardiovascular outcomes are associated with these variants, which additional genetic variants or multi-level environmental factors play a role in phenotypic differences, and the possible roles of ApoL1 genotyping in guiding treatment as well as preventive strategies.
 
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Agenda

Tuesday, June 2, 2015

8:30 am Welcome and Overview – Griffin Rodgers, Director, NIDDK
8:45 am Keynote Address
Feroz Papa, UCSF – When good proteins behave badly
9:30 am Function of ApoL1 – Cell Biology
Larry Holzman, Univ. of Penn. & Ora ​Weisz, Univ. of Pitts.
(15 min. talk, followed by 15 min. discussion)
      9:30 am
      9:45 am
      Katalin Susztak, Univ. of Penn. – Renal cell biology of ApoL1
      Q/A
      10:00 am
      10:15 am
      Martin Pollak, Harvard Univ. - Pathophysiology of ApoL1 kidney disease
      Q/A
      10:30 am
      10:45 am
      John C. Edwards, St. Louis Univ. - Chloride channel activity of ApoL1
      Q/A
      11:00 am
      11:15 am
      Erica Davis, Duke Univ. - Zebrafish models of ApoL1
      Q/A
11:30 am Break
11:45 am Function of ApoL1 – Lipoproteins
Rebekah Rasooly, NIDDK & Katalin Susztak, Univ. of Penn.
(15 min. talk, followed by 15 min. discussion)
      11:45 am
      12:00 pm
      Dan Rader, Univ. of Penn. – Apolipoproteins, lipids and CVD
      Q/A
      12:15 pm
      12:30 pm
      Teepu Siddique, Northwestern Univ. - Apolipoproteins including ApoL1 and ALS
      Q/A
      12:45 pm

      1:00 pm
      Stefan Somlo, Yale Univ. – Teasing out function of disease proteins,
      using polycystin as an example

      Q/A
1:15 pm Lunch
2:15 pm Epidemiology and Genetic Epidemiology
John Sedor, Case Western Res. & Nancy Cox, Vanderbilt
(15 min. talk, followed by 15 min. discussion)
      2:15 pm
      2:30 pm
      Allison Ashley-Koch, Duke - ApoL1 as risk factor for sickle cell nephropathy
      Q/A
      2:45 pm

      3:00 pm
      Alex Reiner, Univ. of Washington – Genetic epidemiology of kidney
      disease in Sickle Cell Diseas
e
      Q/A
      3:15 pm
      3:30 pm
      Karl Skorecki, Technion, Israel - Genetic epidemiology of ApoL1 kidney disease
      Q/A
      3:45 pm
      4:00 pm
      Cherie Winkler, NCI - Population genetics of ApoL1 risk alleles
      Q/A
4:15 pm Break
4:30 pm Translational research  
Karl Skorecki, Technion & Stefan Somlo, Yale
(15 min. talk, followed by 15 min. discussion)
      4:30 pm
      4:45 pm
      Randall Peterson - Screening for small molecule therapeutics in zebrafish
      Q/A
      5:00 pm
      5:15 pm
      Annette MacLeod, Univ. of Glasgow – Trypanosomes and host genetics
      Q/A
7 pm Keynote, introduced by Robert Star, NIDDK
Sarah Tishkoff, Univ. of Penn. - Balancing selection for disease alleles
7:45 pm Panel Discussion
Panelists - TBN
8:30 pm Poster session
   

Wednesday, June 3, 2015

8:30 am Keynote Address, introduced by Marva Moxey-Mims, NIDDK
Lainie Friedman Ross, Univ. of Chicago – Ethical and policy issues related to using complex genetic information in treating complex disease
9:15 am ApoL1 – prevention and health disparities
TBD & Jeffrey Kopp, NIDDK
(15 min. talk, followed by 15 min. discussion)
      9:15 am
      9:30 am
      Erwin Bottinger, Mt. Sinai School of Med. - Screening patients for ApoL1 risk alleles
      Q/A
      9:45 am
      10:00 am
      Charmaine Royal, Duke Univ. - TBD
      Q/A
      10:15 am
      10:30 am
      Neil Powe, UCSF - Health disparities and ApoL1 disease
      Q/A
10:45 am Break
11:00 am Renal Transplantation and ApoL1
Paul Kimmel, NIDDK & Barbara Murphy, Mt. Sinai School of Med.
(15 min. talk, followed by 15 min. discussion)
      11:00 am

      11:15 am
      Dan Brennan, Wash. Univ. - Kidney Transplant Perspectives: HIV and
      other viruses, what we know and what we need to know

      Q/A
      11:30 am
      11:45 am
      Dave Wang, Wash. Univ. - Polyoma virus
      Q/A
      12:00 pm
      12:15 pm
      Barry Freedman, Wake Forest Univ. – ApoL1 and kidney transplantation
      Q/A
      12:30 pm
      12:45 pm
      Jack Stapleton, Univ. Iowa – Viral coinfection: GB C virus and HIV
      Q/A
1:00 pm Lunch
2:00 pm Risk factors
Barry Freedman, Wake Forest Univ. & Cherie Winkler, NCI
(15 min. talk, followed by 15 min. discussion)
      2:00 pm
      2:15 pm
      Lindsay Farrer, Boston Univ. – Genetic modifiers of disease
      Q/A
      2:30 pm
      2:45 pm
      Akinlolu Ojo, Univ. of Michigan - H3Africa and H3Kidney
      Q/A
      3:00 pm
      3:15 pm
      Michael Ross, Mt. Sinai School of Med. – HIVAN – a 30 year perspective
      Q/A
3:30 pm The way forward
Robert Star, Director, DKUHD, NIDDK
Discussants - TBN
   
​​​

Directions/Travel

College Park Marriott Hotel & Conference Center

Hyattsville, MD
June 2 – 3, 2015

Air Travel
Travel arrangements are your own responsibility, but you should know that three airports (listed below) serve the Washington, DC, metropolitan area. Please make your own air or rail reservations.

If you decide to extend your stay to take advantage of lower fares, DC-area attractions are only a short distance away from the host hotel.

Hotel and travel information are listed below.

Accommodations
A block of sleeping rooms has been reserved at the following hotel:

College Park Marriott Hotel & Conference Center
3501 University Boulevard, East
Hyattsville, MD  20783
Telephone: (301) 985-7300 or (800) 228-9290
Fax: (301) 985-7517

Website:  http://www.marriott.com/hotels/travel/wasum-college-park-marriott-hotel-and-conference-center/
(More hotel information can be obtained from this website.)

A limited number of sleeping rooms for conference participants has been reserved at the College Park Marriott Hotel & Conference Center. The rate is the prevailing government rate of $199 per night for single occupancy, plus tax (6%). To reserve a hotel room at the group rate, call reservations at
(800) 228-9290 and identify yourself as a member of the ApoL1 and Kidney Disease Meeting, or book online at Marriott​. The room block will be in effect at the government rate only until MONDAY, MAY 11, 2015, or until full, whichever comes first. Any room reservations received after this date will be accepted on a space- and rate-availability basis. Reservations should be made for arrival on June 1, 2015, with departure on June 3, 2015. If you require alternate dates, please send an email to John Hare of The Scientific Consulting Group, Inc. (SCG) at jhare@scgcorp.com. Any alternate date requests will need to be approved through the NIDDK.

Please be certain that the hotel provides you with a confirmation number for your reservation. After
May 11, 2015, the official room block will be released, and the hotel may charge significantly higher rates and may be sold out. When making a reservation, please provide your room and bedding preferences. The hotel will assign specific room types at check-in, based on availability. Please be advised that requests are not guaranteed. Check-in time is 3:00 p.m., and checkout time is 12:00 p.m. If you need to cancel your reservation, please do so by 3:00 p.m. on the day prior to your scheduled arrival, or you will be charged a no-show fee for 1 night on your credit card.

Taxi Service to the Hotel

From Ronald Reagan Washington National Airport (DCA):
Approximate hotel distance and direction: 15 miles northeast
Estimated Taxi Fare: $60

From Baltimore/Washington International Thurgood Marshall Airport (BWI):
Approximate hotel distance and direction: 30 miles southwest
Estimated Taxi Fare: $65

From Washington Dulles International Airport (IAD):
Approximate hotel distance and direction: 50 miles northeast
Estimated Taxi Fare: $80

All three airports have taxis available and waiting.

SuperShuttle
SuperShuttle offers service to most hotels from Ronald Reagan Washington National Airport, Washington Dulles International Airport, and Baltimore/Washington International Thurgood Marshall Airport. The shuttle leaves on an as-needed basis between the hours of 5:30 a.m. and 11:00 p.m. During other times, arrangements for a shuttle can be made by calling (800) 258-3826 from the airport, or visit their website at http://supershuttle.com.

Driving Directions

From Baltimore/Washington International Thurgood Marshall Airport (BWI):
Take I-95 South to exit 27(495 West/US 1). Stay left immediately after the split and follow signs to
Rt. 1 College Park. Take Exit 25B to US 1 South, and travel .9 mi. Take the ramp onto Route 193 West, and at the 3rd traffic light (Adelphi Road), make a U-Turn. Take an immediate right onto the UMUC Campus. Follow the signs to the Inn & Conference Center.

From Washington Dulles International Airport (IAD):
Follow signs to Washington, DC, via the Airport Access Rd. Take I-495 East (toward Baltimore). Stay on I-495 E and exit onto New Hampshire Avenue South (Exit 28B). Turn left at the 2nd light (Adelphi Road). Go 3 miles. At the intersection of Adelphi Road and Route 193, turn left onto Route 193 (University Boulevard), then make an immediate right onto the UMUC Campus. Follow the signs to the Inn & Conference Center.

From Ronald Reagan Washington National Airport (DCA):

Take the George Washington Parkway North to I-495 East, (toward Baltimore). Stay on I-495 E and exit onto New Hampshire Avenue South (Exit 28B). Turn left at the 2nd light (Adelphi Road). Go 3 miles. At the intersection of Adelphi Road and Route 193 (University Boulevard), turn left onto Route 193 (University Boulevard), then make an immediate right onto the UMUC Campus. Follow the signs to the Inn & Conference Center.

Parking
The hotel provides complimentary on-site parking for meeting participants.​

Minutes

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

ApoL1 and Kidney Disease Conference  

College Park Marriott Hotel & Conference Center
Hyattsville, MD
Jun 2 - 3, 2015

Experiments and Areas of Research Suggested by Participants

Clinical/Human subjects research

Franceschini
Characterization of ApoL1-related CKD in African American populations without and with CKD, such as to identify factors (environmental and genetic) that contribute to disease - Or even better, that are associated with no transition to disease. Who are these healthy individuals who are carriers of ApoL1 2 risk alleles, and what was their lifetime exposure experience? It would be of interest to know their trajectory in birth cohorts, studies of pregnancy and in children. Ideally, we should be using our best approaches in epidemiology/clinical research for that including longitudinal studies, both in established cohorts with standardized measures and rich environmental factors (including accounting for SES, co-morbidities, toxins), but also using EMR samples so to capture treatment, and medical resource use.

Franceschini
Apply findings from basic research in clinical/epidemiological research - for example, if there is evidence for a mechanism related to lipids, we could look at this in our studies. If the protein is harmful to podocytes, should we be checking UACR in African Americans?

Le
Assess genetic factors which modify the influence of ApoL1 high risk variants on the course of kidney disease progression and on plasma levels of markers of oxidative stress and apoptosis - Genetic modifiers may provide meaningful information regarding pathways regulated by the gene of interest, as well as modifiable factors for therapeutic target. In this regard, our preliminary data show that the GSTM1(0) and the ApoL1 high risk alleles confer additive deleterious effects in AASK participants. Interestingly, those with ApoL1 high risk alleles but homozygous for the GSTM1 active allele (GSTM1 1/1) appear to be protected from CKD progression. In addition, we find that Gstm1 knockout mice have significantly increased levels of superoxide in the kidney, and worse kidney injury in angiotensin II-induced hypertension than wild-type mice. The deleterious additive effect of GSTM1(0) allele to worsen clinical outcomes in AASK participants carrying the ApoL1 high risk alleles may suggest that ApoL1 influences oxidative stress. Oxidative stress and apoptosis are closely linked biological processes. Moreover both oxidative stress and apoptosis have been linked to chronic kidney disease. The joint effects of GSTM1 and ApoL1 on clinical outcomes and markers of oxidative stress and apoptosis should be examined in CKD patients.

Ashley-Koch
Expand metabolomics work both in SCD-CKD [Sickle Cell Disease-Chronic Kidney Disease] cases and in non-SCD CKD cohorts – this will allow investigators to sort out what signals may be specific to the ApoL1 risk variants and what may be distinct in SCD vs. non-SCD.

Reidy
Effect of ApoL1 on birth outcomes and nephron number – Is this a direct effect or is prematurity/low nephron number a second hit resulting in ApoL1 disease? If it affects perinatal/birth outcomes there is a potential for tighter screening and intervention. If prematurity is a risk factor it provides a new tool to understand which premies need to be followed for renal issues (there are no current recommendations of how premies should be followed for renal issues beyond checking blood pressures in the first 2 years of life). The way to study this is to examine a perinatal/neonatal cohort, collect placentas, maternal and baby DNA and pregnancy outcomes (preeclampsia/eclampsia)/ neonatal outcomes (prematurity). The goal would be to enroll all early in pregnancy and there will be a subset with fetal demise and neonatal deaths and one could do nephron (and podocyte) counts on those kidneys. There could then be longitudinal followup to assess who develops disease. There is as an active effort nationally to develop neonatal cohorts and this would fit in well.

Freedman
Identification of non-HIV viruses that may serve as second hits in ApoL1-nephropathy - these might be amenable to treatment to slow nephropathy progression. This project involves looking at urine and kidney tissue (possibly blood also).

Sampson
GWAS using ‘super-controls’ - Identify a cohort of older African-American individuals with 2 risk alleles who do not have any sign of kidney disease (normal eGFR, no proteinuria) and perform a GWAS of this group of “super-controls” versus African-Americans with FSGS and 2 risk alleles. Collect detailed histories from these cases and controls in terms of environmental and infectious exposures as well as characteristics such as birth history and their BMI. The hypothesis would be that we could identify genetic or environmental differences between these two groups that teach us about factors that either potentiate or protect against the development of ApoL1-associated proteinuric disease.

Transplant

Franceschini
ApoL1 genotyping for prognosis - Evaluate the benefits/costs of genotyping African American (and Hispanic) donors for prognosis, considering the ethical and cost issues. It would be interesting to have some cost analysis done for this purpose.

Freedman
Prospective study of African American deceased kidney donor ApoL1 genotypes and their recipient ApoL1 genotypes - with testing for interactions between them. Donor kidney tissue ApoL1 protein and mRNA should also be assessed at the time of initial transplantation for effects on allograft survival.

Doshi
Investigate African American live kidney donors - are they at an increased risk of developing hypertension and ESRD than age-, gender-, race- and time to follow-up matched healthy controls (non-donors)? Can this increased risk can be explained by familial/genetic factors i.e. ApoL1 risk alleles that are shared between the donor and the recipient (absent in the non-donor, control group)? Use historical and prospective living kidney donors to:
  • Compare the post-donation incidence of hypertension and trajectory of blood pressure between donors with two versus zero/one APOL1 risk alleles.
  • Compare the trajectory of post-donation renal function between donors with two versus zero/one APOL1 risk alleles.
  • Collect samples from donated organ for study of podocyte injury

Basic

Pollak
ApoL1 toxicity - conduct ApoL1-mediated cell toxicity assay for small molecules which rescue the G1 and G2 associated lethality. Rationale: ApoL1 risk variants never would have been discovered without non-hypothesis based experiments. Now everyone is pursuing the same one or two pathways for mechanism. A non-hypothesis based mechanism screen is needed to identify new pathways.

Weisz
What is the basis for ApoL1 toxicity? - For example, do podocytes or other possible affected cell types with one or two variant allelles have altered lysosomal pH? Are there altered lysosomal or ER stress responses in these cells? What modifies expression of ApoL1?

Le
Use healthy kidney tissues obtained from donor kidney immediately prior to implantation to determine the differences in gene expression networks and epigenetics influenced by ApoL1 G1/G2 risk variants versus the G0 variant - Gene expression networks and epigenetics may provide mechanistic role of a gene of interest when appropriate or ideal animal models are not available. However, gene expression and epigenetics are influenced by disease states, and therefore alterations in their profiles may reflect more of a response to disease rather than direct effect of the gene of interest. Use of healthy kidney tissues from donor kidney carrying the ApoL1 high risk variants to determine changes in gene expression networks and epigenetics would be more advantageous than using “normal kidney area” from kidneys removed from patients with to renal neoplasms to avoid the possibility of gene expression changes in “normal tissue” that could result from paracrine effects of or response to the nearby tumor.

Edwards
Establish the sub cellular membrane fraction in which ApoL1 resides in human podocytes - isolate that membrane fraction from cells expressing the various forms, and assess transport/permeability/channel properties of the protein.

Fornoni
Cholesterol and ApoL1 - Data suggest that accumulation of cholesterol in podocytes in CKD causes podocyte injury and that cells expressing G1 or G2 variants accumulate intracellular cholesterol. How do ApoL1 risk alleles influence cholesterol efflux from cells? As we do not know if cellular specific or circulating ApoL1 is important, then there are two key experiments. One is to test cholesterol efflux from WT macrophages exposed to the sera collected from patients with different risk alleles and the other is to test cholesterol efflux in macrophages isolated from patients with different risk alleles.

Fornoni
Use of iPS [induced pluripotent stem cells] - Develop iPS-derived human podocytes modified by genomic editing to express the different ApoL1 risk variants and use for testing cholesterol efflux.

Weisz
Site of action of ApoL1 - What is the primary affected cell type relevant to ApoL1-associated CKD? Endothelial cells, podocytes, proximal tubule cells?

Weisz
Cell biology of ApoL1 - Are there structural changes in G1 and G2 that affect folding/stability/membrane insertion? Given that the protein has no disulfides or glycans it would appear that it can more easily escape ER quality control mechanisms than other secreted proteins. What is the trafficking route/stability of ApoL1 in cells? Can endogenous ApoL1 cause cellular changes? What is the cellular site of action? If it’s lysosomes, how does newly synthesized ApoL1 get to this compartment? Cells typically work hard to shunt their secreted proteins away from lysosomal routes, although it’s possible that the protein is associated with membranes and percolates passively into lysosomes where it is activated where it may be activated. Do the variants cause trouble because they don’t insert as well into lipoprotein particles and/or are more likely than G0 to be “free” in the bloodstream? Do they associate better or worse than G0 with lipids?

Weisz
Second hits – It is unlikely that second hits affect the ApoL1 target cells directly, so how do they synergize systemically with G1 and G2 to propel disease progression?

Ashley-Koch
Zebrafish models of ApoL1 - Create a zebrafish ApoL1 CRISPR mutant on a fli1-eGFP reporter line background so that we can investigate the potential effects on vascular endothelial cells and determine what that relation is to the kidney phenotypes. In addition, create a zebrafish APOL1 CRISPR mutant on the pod-NTR-mCherry background so that we can flow sort the podocytes and further investigate gene*gene interactions, through RNAseq.

Susztak
Determine the critical cell type(s) for APOL1-mediated disease development - characterize the phenotype of transgenic mice with podocyte, tubule epithelial cell, liver, endothelial and vascular smooth muscle specific inducible reference (G0) and risk allele (G1 and G2) ApoL1 expression. Our preliminary experiments indicate that podocyte specific, but not tubule specific, risk allele ApoL1 induces nephrotic syndrome and glomerulosclerosis in mice. While most human cells can express ApoL1, we propose that the phenotype heterogeneity might be related to cell type specific expression and regulation of ApoL1. For example while podocyte specific risk allele ApoL1 is associated with FSGS development, hypertensive renal disease could be induced by vascular ApoL1 expression. Create and study different mouse lines with cell type specific temporal control of ApoL1 expression, and study expression levels and phenotypes including albuminuria, kidney function, blood pressure, renal histology, podocyte number, hyalinosis, and atherosclerosis.​

Attendees

Attendees are currently unavailable.

Abstracts

Submission Deadline: Friday, May 1, 2015

Participants in the ApoL1 and Kidney Disease, are encouraged to submit abstracts of their research activities. In addition to an opportunity to present their research in a poster session, conference attendees will find additional career development and networking opportunities with other researchers.

All abstracts must be submitted via email to John Hare of The Scientific Consulting Group, Inc. at jhare@scgcorp.com with "ApoL1 Abstract" in the subject line. Abstract submissions should be no longer than 250 words (not including name and affiliation).

Please follow the instructions below to submit an abstract for consideration:

  1. The abstract should be an MS Word document typed single-spaced using 10 point type. The abstract's title should be typed in CAPITAL LETTERS and should clearly represent the nature of the investigation. The title should be followed in lowercase letters by the author's first and last names, degree, and affiliation (if applicable), city, state, and country. Underline the primary author's name (one primary author per abstract). Do not leave spaces between the title and the body of the abstract, or between paragraphs. The abstract file should be saved as: primary authors' last name_first word in the title (e.g., Zucker_Effects).
  2. Please ensure that your abstract is the correct length and use 1" margins.
  3. Use of standard abbreviations is desirable (e.g., RBC) as well as standard symbols for units of measure (e.g., kg, gm, mg, mL, L, and %). Place a special or unusual abbreviation in parentheses after the full word the first time that it appears. Use numerals to indicate numbers except to begin sentences. Do not use subtitles (e.g., Methods, Results).
  4. Simple tables or graphs may be included; however, they must fit within the designated abstract space of one page.
  5. Please use Times New Roman as the font.

Body of the Abstract

  1. Organize the body of the abstract as follows:
  • Statement of the purpose of the study/program/project;
  • Statement of the methods used;
  • Summary of the results presented in sufficient detail to support the conclusion; and
  • Statement of the conclusions reached.

POSTER PRESENTATIONS

Poster presentations will be displayed on 4-foot-high by 6-foot-wide poster boards. Pushpins and Velcro will be provided onsite.

All presenters must pre-register for the conference.

Location

Line
  • MD
Webinar

Contacts

Line ​​For questions concerning program content, contact:

Rebekah S. Rasooly, Ph.D. 
KUH/NIDDK/NIH
Two Democracy Plaza 
6707 Democracy Blvd., MSC 5458 
Bethesda, MD 20892-5458
Phone: (301) 594-6007
Fax: (301) 480-3510; 

For questions concerning meeting logistics, contact:

John Hare, M.S., CMP, CGMP
The Scientific Consulting Group, Inc. 
656 Quince Orchard Road, Suite 210 
Gaithersburg, MD  20878 
Phone: (301) 670-4990 
Fax: (301) 670-3815