Summer Undergraduate Research Fellowship in Pathophysiology, Biology, and Bioenergetics of Renal Diseases

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RESEARCH PROGRAM DESCRIPTION

This summer fellowship research program is a Department of Medicine, Nephrology Section multi-investigator effort of three federally funded research labs who work closely in related fields of interest. With a focus on two common kidney disorders, autosomal dominant polycystic kidney disease (ADPKD) (Drs Chapman, Chen and Muir) and nephrolithiasis (Drs Coe, Worcester, Hassan, Ko, Zisman and Prochaska), students will learn about intestinal and renal regulation of urinary oxalate excretion, metabolomic features of bioenergetics regulation of the kidney, mechanisms of urinary acidification and the impact of the microbiome on a number of these measurements. These programs will provide students an introduction to the field of renal physiology and cell biology in the context of common renal medical disorders. Our curriculum will include weekly meetings with all students present together, with the expectation of a presentation of their ongoing work with their faculty mentors. This seminar will be led by the Chief of Nephrology, Dr. Arlene Chapman, and Dr. Hatim Hassan. Each student will briefly discuss the overall progress of his/her particular lab as well present his/her own summer project. This will be followed by an open discussion where all of the students can discuss the presented data and give questions and answers. This program will be more of a small group tutorial with the opportunity for group mentoring. This will give the students the opportunity to present their work to each other on weekly basis. Additional programmatic ideas for this cohort include the following: 1) Participation in the summer TREKS Nephrology Modules, under the direction of Dr. Ben Ko, which is held for one week each summer with students from throughout North America participating. 2) Attending weekly conferences within the section of nephrology typically held on Thursdays and Fridays. 3) Attending individual lab meetings held weekly or twice weekly by each of the research programs outlined in the application and will also include daily lab work when lab meetings are not being held. 4) shadowing expert clinicians in their weekly clinics on Tuesdays and Wednesdays (Drs. Zisman, Prochaska, and Chapman) to observe patients with underlying kidney problems associated with the research studies in their respective labs. 5) Observation of human subject research on the Clinical Research Center which is a research-only inpatient and outpatient ward studying detailed phenotypes of ADPKD and nephrolithiasis study participants. This is expected to be a wonderful opportunity for this summer cohort. Overall, it is expected that the students in this program will be deeply immersed in their projects during the summer and as time permits throughout the rest of the academic year.

PROJECTS

Project # 1:

Title: Targeting Amino Acid Metabolic Crossroads in ADPKD

Mentors: Arlene Chapman, MD, Alex Muir, PhD, Peili Chen, PhD, Departments of Medicine and Molecular Biology. Drs. Chapman, Muir and Chen will be available and committed to fully mentor the students, including guidance about overall career development.

Project description

Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease, is caused by mutations in the PKD1 or PKD2 gene which encode polycystin-1 and polycystin-2 transmembrane heterodimer proteins. Multiple signaling pathways are affected by mutated polycystin1 and polycystin 2, including primary ciliary signaling and Ca2+/cAMP cascade that contribute to the abnormal proliferation of epithelial cells and cyst formation in ADPKD. Initiated in early childhood, progression of renal cysts gradually damages kidney structure and function, eventually leading to renal failure typically in the 5 to 6th decade of life. Despite promising results from recent studies and trials, therapies that cure or slow the progression of disease are limited. The slow progressive nature of ADPKD make it difficult to diagnose and treat at early stage as the estimated glomerular filtration rate (eGFR) is normal for decades. Height corrected total kidney volume (htTKV), an accurate and reproducible FDA approved imaging prognostic biomarker can increase several-fold prior to loss of kidney function and represents cyst burden and epithelial proliferation. However, measurement cyst burden through HtTKV using magnetic resonance imaging (MRI) is only useful in the setting of macroscopic cysts which have been developing for decades. Candidate biomarkers have been evaluated in urine and plasma from ADPKD patients including neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein (MCP)1 and CD14, as well as non-targetted profiling of urinary proteome and miRNAs however their contribution to understanding the progression of ADPKD or strength as a biomarker are not additive to htTKV.

Increasing understanding of the signaling and pathological derangements characteristic of ADPKD has revealed marked similarities to those of cancers at the cellular and molecular level. ADPKD shares most of cancer hallmarks including sustained proliferative signaling, evasion of growth suppressors, induction of angiogenesis, deregulation of cellular energetics, tumor-promoting inflammation, genomic instability and mutation and abnormally reprogrammed metabolism. Metabolic reprogramming provides energy and substrates that is necessary to support tumor growth, survival, immune evasion, and metastasis. Recent studies in PKD1 cells demonstrate a Warburg-like effect as observed in cancer cells, which when inhibited results in inhibited cell proliferation and decreased cyst growth and TKV. This metabolic change is also observed in cystic epithelia in ADPKD patient kidneys, indicating altered bioenergetics and adaptation supporting a proliferative cystic phenotype in ADPKD.

We have demonstrated comprehensive abnormalities in multiple amino acid concentrations and metabolic pathways in our studies in urine and plasma in ADPKD patients with normal kidney function, particularly the histidine pathway. Furthermore, levels of histidine metabolites correlate with cyst burden (htTKV) and kidney function (eGFR). In ADPKD cyst fluids, concentrations of all amino acids, except for Glutamine and Proline, are elevated compared to those in plasma and urine, suggesting that active accumulation of amino acids on the apical surface of cystic epithelia occur. Pharmacologically targeting histidine metabolism at histidine decarboxylase or histidine ammino-lysase affects cystic cell proliferation but not healthy non-cystic human epithelia, indicating a possible therapeutic role in the treatment of this disorder.

Specific Aims

To determine the effects of loss of the PKD1 or PKD2 genes on amino acid (specifically histidine) metabolism, transport and flux.

Approach and Methods

To investigate histidine homeostasis by evaluation of histidine transporters in small intestinal epithelia, hepatocyte and renal cystic (PKD1 or PKD2 mutations) compared to normal non-cystic epithelia. Expression and function of histidine transporters will be studied in tissues and specific cell types including resident macrophages, fibroblasts, cystic and non-cystic epithelial cells harvested from genetically modified mice using immunostaining and affinity assays.
To characterize histidine and its metabolic flux into different pathways in PKD1 and PKD2 knockdown cells established by siRNA using stable isotopic 13C-histidine.
To define difference in energy production from histidine in PKD1/PKD2 cells compared to normal non-cystic controls under controlled environmental conditions including cell starvation and hypoxia.

Project # 2:

Title: Oxalobacter formigenes-derived peptides impacting Hyperoxalemia, Hyperoxaluria, and related Kidney Stones

Mentor: Hatim Hassan, MD, PhD, John Alverdy, MD, and Matthew Tirrell, Departments of Medicine and Surgery and Institute of Molecular Engineering. Drs. Hassan, Alverdy, and Tirrell will be available and committed to fully mentor the students, including guidance about overall career development.

Project Description:

Kidney stones (KS) affect ~1 in 5 men and ~1 in 11 women, are costly (>$10B annually), and are associated with CKD and ESRD. High recurrence rates (50% in 5 years and up to 80% in 10 years), indicate that current interventions are inadequate and alternative therapies are needed. Most KS are composed of calcium oxalate and very small increases in urine oxalate concentration increase the risk for stone formation. Lower urinary CaOx supersaturation definitively reduces KS formation. Currently, no FDA approved drugs reduce urinary oxalate excretion. The gut bacterium Oxalobacter formigenes (Of) induces colonic oxalate secretion and reduces urinary oxalate excretion via an unknown secretagogue. Given the difficulties with recolonization, Of alone is not therapeutically feasible and underscores the need to identify the secretagogue that induces colonic oxalate secretion. To this end, we have identified Of-derived factors secreted in its culture conditioned medium (CM) that significantly stimulate (>2.8-fold) oxalate transport by human intestinal Caco2-BBE (C2) cells through PKA activation and stimulation of the oxalate transporters SLC26A6 (A6) and SLC26A2 (A2). In vivo, rectal administration of Of CM reduced urinary oxalate excretion > 32.5% in hyperoxaluric mice, and stimulated colonic oxalate secretion >42%, reflecting the potential therapeutic impact of these factors. We identified a family of a signaling protein as the major Of-derived factors. These proteins closely recapitulate the effects of the Of-derived factors and similarly stimulate (1.4-2.4-fold) oxalate transport by C2 cells. We also identified 35-amino acid peptides (P7-10) within one protein that significantly stimulate (1.5-fold individually and >2.4-fold by P8+9) oxalate transport by C2 cells. Importantly, P8+9 peptides significantly stimulated oxalate transport by HUMAN sigmoid colon (1.8-fold), distal colon (1.7-fold), and ileum (2-fold) organoids (ex vivo intestinal epithelia models fully mimicking the in vivo physiological responses), confirming that P8+9 peptides work in human tissues and that they will likely stimulate oxalate secretion in human colonic and ileal epithelia in vivo. Identification and characterization of the active motifs responsible for colonic oxalate transport can ultimately be translated into an effective novel therapeutic targeting the reduction of plasma and urine oxalate levels. I founded a startup company (Oxalo Therapeutics) to help with developing these peptides into a peptide-based therapeutic and obtained an NIH fast-track STTR grant to optimize our lead peptides through structural modifications (some of which had already being completed). We also obtained phase I NSF STTR grant to develop an innovative drug delivery system consisting of peptide-loaded hydrogel nanoparticles (PLHN) as a vehicle to deliver novel peptides to the intestinal epithelium. Once delivered, the nanoparticles will adhere to the intestinal mucosa and slowly release the peptides, stimulating intestinal oxalate secretion, thereby lowering plasma and urine oxalate and hence preventing KS formation. Such delivery will enable P8+9 peptides to immediately act on the intestinal epithelium to induce oxalate secretion, before being degraded by proteolytic enzymes, mimicking of behavior. In collaboration with Dr. Matthew Tirrell, we are also developing P8 and P9 peptide amphiphiles (peptide-based micellar constructs which can be an effective carrier vehicle for therapeutic drugs) for in vivo testing.

Specific Aims:

Evaluate whether the optimized P8+9 peptides, P8+9 PLHN, and P8+9 peptide amphiphiles (administered rectally as enemas) will reduce plasma and urinary oxalate levels in hyperoxalemic and hyperoxaluric mice.
Develop enteric coated capsules containing the optimized P8+9 peptides, P8+9 PLHN, and/or P8+9 peptide amphiphiles for oral administration and evaluate their therapeutic potential in the above mice.
Identify the shortest functional P8 and P9 peptides subdomains by deleting specific amino acid residues.
Identify and characterize the involved cell surface receptors in C2 cells.
Characterize the involved signaling pathways in C2 cells.

Approach and Methods:

Following collection of baseline urine, blood, and fecal samples (for oxalate measurements), hyperoxalemic and hyperoxaluric mice will be given the optimized P8+9 peptides, P8+9 PLHN, P8+9 peptide amphiphiles, or vehicle twice daily for 3-4 weeks via intrarectal administration. At the end of treatment periods, urine, blood, and fecal samples will be collected for oxalate measurements and intestinal tissues (ileum, cecum, proximal, and distal colon) will be isolated and mounted in Ussing chambers to assess whether any observed reduction in plasma and urinary oxalate levels is due to enhanced intestinal oxalate secretion. Seeing enhanced secretion, the expression of the oxalate transporters A1, A2, A3, and A6 in intestinal tissues will be assessed using qpcr, immnunocytochemistry, and immunoblotting. The capsules will be given by oral gavage (twice daily) for 3-4 weeks and similar studies will be done as described above. The effects of truncated and full-length P8 and P9 on oxalate transport by C2 cells will be compared to identify the shortest functional P8 and P9 peptides subdomains.

Project # 3:

Title: Diet Acid-Base Balance in Patients with Calcium Kidney Stone Disease

Mentors: Fredric Coe, MD, Elaine Worcester, MD, Ben Ko, MD, Anna Zisman, MD, Megan Prochaska, MD. Department of Medicine. Drs. Coe, Worcester, Ko, Zisman and Prochaska will be available and committed to fully mentor the students, including guidance about overall career development.

Project Description

Diet sodium and acid intake strongly affect mineral metabolism and risk for kidney stone formation. Acid loads raise urine calcium losses, saturating urine with stone forming calcium salts, and foster bone mineral loss. The effects are most severe in those people with inherited hypercalciuria, a polygenic trait that makes calcium balance and urine calcium loss abnormally responsive to both salt and acid load. We have found that patients who make calcium phosphate stones, and women who make calcium oxalate stones, have abnormalities of acid-base status, compared to same-sex normal subjects. We have also discovered differences in acid-base handling that involve both gastrointestinal system and kidney in normal men and women. Funded by an NIH Program Project grant (Worcester, PI) the group presently studies effects of varying diet sodium and alkali supplementation on renal calcium handling in the University of Chicago Clinical Research Center.

A full understanding of acid-base balance requires a complete accounting for all renal acid excretion, which is not obtainable from standard urine measurements. In order to better understand the abnormalities we have seen in various types of stone formers, as well as the differences in acid-base handling between normal men and women, we have added novel measurements of urine anion excretion that are the effectors of acid production from diet. We are studying these anions in response to altered diet sodium and alkali, in both types of calcium stone formers and normal subjects. To complement our new measurements, we plan metabolomic measurements of urine anion patterns in collaboration with Dr. Arlene Chapman’s group.

Our previous work has shown differences in segmental renal tubule handling of sodium and calcium between normal subjects and stone formers, which foster loss of calcium in the urine. As there is no appropriate animal model of human stone formation, it has been difficult to examine the possible differences in renal tubule transporter abundance or function that may create the altered mineral handling. Dr. Ko has recently applied the techniques of urine exosome analysis to characterize how nutrient ingestion alters renal transporters, by measuring the levels of transporters of interest in urine exosomes during nutrient challenges.

Specific Aims

Identify and quantify the differences in renal tubule sodium and calcium handling between calcium stone formers and normal subjects under conditions of high and low salt intake, with or without alkali.
Quantify the differences in renal tubule transporter abundance between calcium stone formers and normals under conditions of high and low salt intake, with or without alkali.
Quantify the differences in acid-base handling between normal subjects and calcium stone formers using standard measurements of acid excretion and titration of urine organic anions.

Approach and Methods

Calculate proximal and distal nephron sodium and calcium reabsorption using endogenous lithium clearance in normal men and women and in men and women with calcium oxalate or calcium phosphate stones on each of 4 diets. Diets will be low sodium or high sodium, with 20 meq potassium citrate daily or placebo, in random order.
Measure urine exosome levels of NHE3, SLC26A6, claudin 2, NKCC2, Claudin 14, NCC, TRPV5 and prostasin in patients in aim 1.
Measure urine markers of acid and alkali balance and urine organic anions by titration, in stone formers and normal subjects, and calculate acid balance.

MENTORS

Names, qualifications and delineation of roles of proposal mentors/leaders:

Arlene Chapman, MD, Professor of Medicine, Chief of Nephrology. Directs the ADPKD center of excellence, with NIH funding for over 18 years in the study of ADPKD. She has over 2200 ADPKD patients in her program where students will learn about the clinical manifestations of the disease and apply them to the proposed laboratory experiments. She will lead the conceptual development of projects with the investigative team along where the students will participate.
Peili Chen, PhD, Research Associate: Cell and Molecular biologist, working with genetic murine and cultured cell models of PKD, experienced in cell metabolism and mitochondrial homeostasis in hypoxic and normoxic conditions, and will mentor studies in cell proliferation, bioenergetics, metabolomics, PKD mouse models, tissue harvesting, and amino acid transporter immunohistochemistry and HPLC analyses.
Alex Muir, PhD, Ben May Department of Cancer Research, trained investigator in Krebs cycle intermediates, mitochondrial function, bioenergetics and amino acid transport and cellular uptake, will be responsible for providing mentorship in nutrient studies, histidine uptake, krebs cycle intermediates as they relate to reduction in polycystin levels.
Hatim Hassan, MD, PhD, Associate Professor of Medicine: A well trained investigator in epithelial transport (with specific expertise in gastrointestinal oxalate transport and its relevance to overall oxalate homeostasis), cell signaling, biochemistry, and molecular biology. He will lead the conceptual development of projects with the investigative team along where the students will participate.
John Alverdy, MD, Sarah and Harold Lincoln Thompson Professor of Surgery and Executive Vice-Chair of the department of surgery at UOC. Dr. Alverdy is the director of the Center for Surgical Infection Research at UOC that studies the microbial pathogenesis of infections that develop following surgery including sepsis, wound infection, and anastomotic leak. He has been funded by the NIH for this work since 1999. He will provide mentorship in studies related to the in vivo administration of peptide-loaded hydrogel nanoparticles.
Matthew Tirrell, PhD, dean of the Pritzker School of Molecular Engineering at UOC. He is a pioneering researcher in the fields of biomolecular engineering and nanotechnology, with expertise in peptide-based micellar constructs (amphiphiles) where the dense presentation of a functional peptide at the micelle surface improves the interaction of nanomaterials with cells. He will provide mentorship in studies related to the development of P8 and P9 peptide amphiphiles.
Fred Coe, MD, Professor of Medicine and Physiology. The founder of the Kidney Stone Program at UCM, with over 40 years of continuous NIH funding for the study of the pathophysiology of kidney stones. He will mentor the students in the performance and analysis of studies of acid-base handling in normal subjects and kidney stone patients, including laboratory measurements, data management, analysis and the implications for altered physiology.
Elaine Worcester, MD, Professor of Medicine, is an NIH-funded clinical investigator leading studies of altered renal mineral handling in patients with kidney stones and normal subjects and will mentor the students in the design, performance and analysis of human studies, and the ethical implications of human research.
Ben Ko, MD, Associate Professor of Medicine, has expertise in isolation of urine exosomes and their use to understand alterations of renal tubule specific transport activity in humans under varying dietary conditions. He will provide mentorship in the relevant laboratory techniques and their interpretation as part of studies of human renal mineral handling in health and disease.
Anna Zisman, MD, Associate Professor of Medicine, is a funded investigator with active clinical and research interests in kidney stones and chronic renal disease. She has been recognized for her excellence in teaching and clinical care with several awards, and is the director of the Nephrology Fellowship Program.
Megan Prochaska, MD, MPH, Instructor of Medicine, is a young investigator with clinical and research focus in kidney stones. She has a background in epidemiology, and is now studying the effects of the microbiome on risks for kidney stone disease.

PREVIOUS STUDENTS' FEEDBACK

Summer fellowship mid-term evaluation by the students (referred to here as S1-7):

Usefulness of the specific program elements and whether they are meeting your educational goals!

S1: I think that both individual lab-wise and as an entire fellowship group, there is enough specificity in the topics we cover respectively, and I like that despite the differences in their focus, there are connections made between the topics that make the whole experience cohesive. I think the future journal clubs will help with that as well.

S2: The lectures have been very educational and I really like them. Although we haven't gotten the chance to attend the clinical zooms, I'm really excited for those.

S3: This course is thoroughly meeting my educational goals. Prior to its start, I had hoped to learn more about the processes involved in metabolomics analysis. However, with the lectures, journal clubs, and additional activities like that planned by Dr. Worcester, I have learned a lot more about the kidney itself and the multiple areas of research being conducted in the Department of Nephrology as a whole.

S4: I feel that every element of this program has provided important benefits to my experience this summer. The lectures have given important background about the renal system, both its basic function and structure as well as relevant pathologies. Meanwhile, my project has been an amazing first exposure to clinical studies, and it has provided me with my first real experience of leading a project. And the journal clubs have improved my ability to understand and analyze scientific papers. Overall, I am extremely satisfied with the educational gain from this program, especially considering the fact that it has been remote.

S5: Having feedback from mentors is incredibly helpful. Another feature I liked were the group meetings centered around presentations, because they are a bit more active than listening to lectures.

S6: I think the program is overall very useful to meeting my educational goals as the lectures cover a wide range of material that connect to what we’re working on in either labs or journal clubs.

S7: I thoroughly enjoy and gain a great deal from every part of the program and they definitely have met, or rather, surpassed my educational goals.

Are the lectures helpful?

S1: The lectures are very enlightening and interesting! I really enjoy them and appreciate being able to get a glimpse into all these scientific and clinical aspects of nephrology/research.

S2: The lectures are very helpful, although I found some of the calculations and statistical aspects to be a bit confusing. Other than that, the lectures were mostly easy to follow.

S3: Very. I found the progression of lectures very helpful, beginning with physiology and larger concepts that would then be useful in understanding journal club presentations and lectures covering clinical aspects of the kidney and kidney malfunctions. Each presenter was able to explain very challenging topics in a way that was easy to digest within an hour time span and was helpful answering any and all questions.

S4: The lectures are very helpful. I thought the layout of starting with general renal lectures and then going into specific topics/pathologies later on was very beneficial. I feel that I have a much better knowledge of the renal system as well as current issues in nephrology.

S5: I have found the lectures on the whole very interesting, I thought the lecture on the metabolomics of viruses particularly fascinating. The lectures given by our faculty were definitely useful and I can see their applications to my own research.

S6: I feel that overall the lectures are useful as they tend to be very informative and focused on information that is applicable to all the labs. I do wish that the later lectures were a bit more interactive as the first ones involved a lot of equations and practice work.

S7: Yes, the lectures help tie in the necessary information to understand the research that the other groups as well as our own group are doing. The guest presenters also have very fascinating research to digest and see how their methods and the idea behind the approach is similar or different to what's being done here in these labs. I think all the lectures were extremely informative whether they be fundamental or supplementary. All were enjoyable! Although, sometimes I wish the guest lecturers would go a little bit slower to walk us through some of their graphs or methods more clearly. But eventually things were cleared up with questions, I always enjoy and learn a great deal from the questions the mentors and peers have to ask.

Overall impression of the course.

S1: Again, I definitely do not mind the format of this course. While there may be a few drawbacks due to this fellowship being a new experience for both those teaching and learning, as well as due to Covid forcing this into an online format, I am still learning so much and benefiting through the experience.

S2: I really like that fact that a lot of new research is introduced to us. They're very interesting to hear about and makes the experience much more refreshing than learning from a textbook.

S3: I have been really impressed with how this course has been structured. I realize that everyone was hoping and planning for a wet lab/lab bench summer experience, but within the timespan that restrictions progressed the mentors were able to put together a comprehensive learning experience that not only expanded our knowledge of the kidney and renal function as a whole but also how various forms of analysis are conducted in order to address and treat different malfunctions of the kidney.

S4: It is a great experience for an undergrad planning to enter the medical/biological field. The ability to work personally with such experienced doctors and researchers is fantastic.

S5: Depending on your lab, it is a lot of work (as is to be expected of a fellowship) but it all feels purposeful and meaningful.

S6: Overall I think this is a pretty amazing program and a great opportunity for students.

S7: I love it. I enjoy it, I soak up all the information I can and I try to relate things to one another to the best of my ability. I love how true the course is to its emphasis on the multi-disciplinary nature of research and how that often times leads to the most revealing and holistic findings. I also think it's fascinating how in our research the gut microbiome plays a role in kidney function which effects the whole body and also that the ADPKD research has a lot of overlap with oxalate/kidney stone research so there is no clear boundary to where one discipline ends and another begins, because much like the reality of the human body, everything overlaps and interacts with everything else.

Having sufficient time with your mentors and receiving appropriate guidance.

S1: Yes, I am able to have sufficient time with my mentors and fellow students, as well as communicate with them regularly to commence our research.

S2: Yes. There have been a lot of chances to work with mentors and receive feedback on our work. It has helped tremendously in putting presentations together and staying on track.

S3: My mentors have been incredibly involved and responsive to any questions and concerns. As a group, we meet nearly every day unless there is a lecture or meeting already scheduled during that time. In these daily check ins, we discuss the portions of our analysis that have already completed and plan the future steps in our research. Our mentors truly want us to understand each aspect of our research and have this be a really beneficial learning experience that we can apply to future research.

S4: Yes, I met often and extensively with mentors. They are truly dedicated to our education and work in this program.

S5: Again, lots of useful feedback from our mentors and we regularly meet with them.

S6: I think mentors are very good at being available. I felt I could always reach someone if I had any questions and we were encouraged to ask questions by email or over the phone.

S7: I definitely feel like I have had sufficient time with my mentor and have always received nothing short of illuminating and deeply helpful guidance.

Likelihood of recommending this course to your peers.

S1: I would definitely recommend!

S2: Very likely.

S3: There is a strong likelihood of me recommending this course to my peers, especially those who are premed like myself or who are interested in pursuing a MD-PhD. As someone who has always known that I wish to pursue a career in medicine, particularly primary care, but not the particular area of practice or if I would also like to conduct research, this course has really increased my interest in nephrology as a whole as well as pursuing research as a part of my occupation. While I can’t speak on the lab experience we were supposed to have, all the mentors have shown such eagerness in advancing our knowledge in the field of nephrology that I have no doubt that the future lab experiences that my peers will have will be incredibly interesting, enjoyable, and beneficial as they continue on with their research.

S4: Would definitely recommend.

S5: I would definitely recommend this course to my peers.

S6: I would very much recommend this course to my peers. I think that overall the material is interesting and can be understood by investing time and taking consistent notes!

S7: I don't stop raving about it, and I don’t plan to stop either. This has been an incredible opportunity and I would definitely recommend it to my peers, in fact I already have numerous times and I will keep doing so.

Any other comments.

S2: I would've liked to learn to do some things hands on. But given our current circumstances, I think this program is the best it can be. I'm very happy with my experience. Scheduling is sometimes confusing. Some of the seminars and their times don't match what we were originally given in the calendar. Occasionally I've had to reschedule things but I totally understand the difficulty of setting a calendar in stone from the beginning.

S3: Not at this time. But thank you to all the mentors who have made this experience so enjoyable so far!

S7: This fellowship was, hands down, the highlight of my year. This was so comprehensive and dedicated to the pursuit of knowledge for the sake of knowledge and placed a very necessary heavy emphasis on critical thinking and biomedical intuition. This was also about educating for the purpose of creating a future of not just well-educated future researchers and doctors, but critical thinkers who seek the answers to not just what, but how and why something works the way it does. If anything, I feel as though I am not doing the whole program justice by asking all the questions on my mind. This has been the most cherished experience I've been lucky enough to have, and that was just with it being online! I simply cannot fathom the joy this would bring me to take part in it in person with all our peers. This has been a great deal stimulating and I am extremely grateful to be a part of it.

BSD summer fellowship final evaluation by the students (referred to here as S1-7):

Usefulness of the specific program elements and whether they are meeting your educational goals!

S1: The work in each smaller group was probably the best part, because of all the (virtually) hands-on research I was able to participate in.

S2: I definitely thought the lectures were super helpful. It was a lot of information to absorb at the beginning since I knew close to nothing about the field but things began to make sense as I was exposed to more of the research and application - things fell into place. The presentations were also really educational since it gave me the chance to analyze and discuss more deeply papers and current research, which helped me process the information much better.

S3: I found the lectures, journal clubs, respective group meetings, and the final presentation all to be incredibly helpful. The first portion of the fellowship that was dedicated to learning more about renal function and the physiology of the kidney successfully provided us with a foundation of knowledge we were able to use to better understand the topics covered in journal clubs as well as interpreting my own research. Thank you to all our lecturers throughout the program! Additionally, I thought that the journal clubs and final presentations were a great learning experience and helped prepare me for similar presentations in the future as I continue on with my research. And as always, my mentors were amazing throughout the 10 weeks of the fellowship. Meeting once a day, they were able to answer any questions I might have had and further observe the analysis my partner and I had completed since our last meeting, providing useful knowledge of the kidney and context for the patterns we began to see.

S4: Both the lectures and the independent project were very helpful towards my educational and career-oriented goals. The lectures gave me a fantastic background in the field of nephrology, which helped guide and shape our independent project. I plan to use this project for my thesis, which I am very excited about. And I also learned a great deal about the patient-doctor relationship, which will be invaluable to my future in medicine.

S5: I thought all of the program elements were useful in completing the goals, specifically the faculty lectures that were directly related to fundamentals of nephrology and kidney disease.

S6: I think the various program elements were really great as they all connected, and I felt I learned a lot of relevant knowledge in the field of nephrology. I loved being able to take lecture material and use it in lab work for presentations or understanding graph results.

S7: I thoroughly enjoyed and gained a great deal from every part of the program and they definitely have met, or rather, surpassed my educational goals. This fellowship was, without a moment's hesitation, the peak of the entirety of my learning experience. This was so well thought out, comprehensive, and dedicated to the pursuit of knowledge for the sake of knowledge. I truly love how much of an emphasis it placed on critical thinking, application of knowledge in the field, and enriching us with biomedical intuition. This was also about educating for the purpose of creating a generation of not just well-educated future researchers and doctors, but critical thinkers who seek the answers to not just what, but how and why something works the way it does.

Are the lectures helpful?

S1: I liked the lectures, as they showed various different parts of the nephrology department.

S2: Yes. I think the first few lectures were a little rough since we jumped right in and I knew almost nothing to start with. Some of the calculations had me really confused. But as I heard more and more on the subject I was able to pick up on what was being discussed and I learned a lot from the lectures.

S3: Please refer to prompt 1. where I discuss how helpful I found the lectures to be! Additionally, I would like to note the usefulness of Dr. Worcester’s activity where we were able to apply much of the knowledge we learned previously in the lectures! It was a nice way to wrap up the more educational portion of our fellowship and consolidate all the new information we had learned in the weeks prior.

S4: Yes, the lectures were extremely helpful at setting up a background of knowledge about nephrology and metabolism. While I learned a decent amount about the structure and functions of the kidneys in my physiology class, this summer's material went above and beyond my previous understanding. However, I do think that the consecutive lectures did make it difficult to stay focused at times. Specifically, the day where we had about 4 or 5 mini lectures in a row which lasted 2-3 hours. I do think that is a bit too long to maintain a strong attention span.

S5: Like I said above, the lectures were very informative, especially when they were supplemented with workshops and applications of the material.

S6: The lectures were beneficial and interesting, and the lecturers always had eye-grabbing material that allowed me to connect to the topics more. I never felt like I had a dull lecture.

S7: Absolutely, the lectures were so useful and helped link together all the necessary information so that we could all understand each other through a sort of universal language. It added more depth to our ability to understand the research that the other groups as well as our own group were doing. The guest presenters also had research that piqued my interest and added layers to the knowledge gained from all other facets of the program. It enabled us to digest and see how their methods and the idea behind the approach is similar or different to what's being done here in these labs. I think all the lectures were extremely informative whether they be fundamental or supplementary. All were enjoyable! Although, sometimes I wish the guest lecturers would go a little bit slower so as not to brush over details they think aren't worth explaining even though they were to an audience member like myself. Eventually things were cleared up with hard hitting questions posed by other research mentors and my peers; I always appreciate and learn a great deal from the questions posed.

Overall impression of the course.

S1: The program was very educationally rich, with a lot of content covered throughout it. I liked well-rounded it was both in terms of format - lectures, small groups, and journal club - and content - ADPKD/clinical vs more scientific research.

S2: I really enjoyed the course, especially the fact that we were presented with a lot of ongoing research and taught to analyze things on our own as opposed to simply being fed the concepts. It made the learning a lot more engaging and I really loved hearing about new research in the field.

S3: I am personally really happy with how the course turned out. I realize that because the fellowship was initially a lab-based experience that the doctors spearheading the program had to make a lot of drastic changes, but they were able to do so successfully and created a multi-faceted learning experiences that supplied the fellows with useful knowledge of nephrology and an excitement to continue on with their research in the future.

S4: The course was fantastic and is a great opportunity for students with medical and research aspirations.

S5: Overall, the course was a really good balance of hands-on work and informative lectures.

S6: I think the course is very strong and makes the field of nephrology very exciting and accessible despite the limitations of online learning.

S7: I loved it a lot. I gained a lot of knowledge and experience and enjoyed it all along the way. I loved how true the course is to its emphasis on the multi-disciplinary nature of research and how that often times leads to the most revealing and holistic findings. For example, I have a huge deal of respect for how my mentor approached a kidney issue from its route cause in the gut utilizing the core reductionist approach to research in biology: breaking down a complex and nebulous issue (which effects the whole body and has ties to ADPKD development) into understandable pieces, progressing step by step into more detailed territory until the solution becomes elucidated, increasingly so with every subsequent part of the process. It really helped me internalize the fact that there is no clear boundary to where one discipline ends and another begins, because much like the reality of the human body, everything overlaps and interacts with everything else.

Having sufficient time with your mentors and receiving appropriate guidance.

S1: Mentors and their guidance were a huge part of the experience and in getting the results we did. We had daily meetings and more if needed, so we had sufficient time.

S2: Yes. We had plenty of opportunities to meet together as a group and receive direct feedback and guidance. Things were always clarified, even multiple times, when something did not make sense. I felt fully supported.

S3: Again, please refer to prompt 1. where I discuss how grateful I am for my mentors’ guidance over the course of the fellowship! I’d also like to note that when my mentors felt that they themselves did not know as much about a topic that my partner and I had questions or concerns about, they were able to bring in an outside specialist in that field to meet with us. Specifically, as we learned how to use the multiple different analysis programs crucial to our secondary data analysis, one of my mentors was able to reach out to an external specialist to walk us through the programs he himself either wrote or had past experiences with. Incredibly helpful!

S4: I was able to talk and meet with mentors on a regular basis, receiving extensive advice and help from both of them. So 5/5 on this aspect of the internship for sure.

S5: My mentors were great and have been incredibly helpful to me

S6: I was always able to reach mentors either in the lecture or by email or phone if needed.

S7: I definitely can say I have had beyond sufficient time with my mentor and have always received nothing short of illuminating and deeply helpful guidance. I really look forward to continuing to learn from my mentor in the future and I genuinely hope to follow in his exact career path footsteps one day. I don't know how the mentors in this fellowship do all that they do, seeing patients in the clinic regularly, having very complex patients under their care, training residents and fellows on the job, taking on intensive and immersive research endeavors, and then going on to not only teach, but be a mentor in the full embodiment of the word to their students, and on top of it all, organize and take part in teaching everything they think we can absorb and more from the most fundamental of concepts to the most complex of mechanisms in a very logical manner. Our mentor especially taught our group both the theory and the practice of his research in spite of the fact that it was an online experience. It was innovative and eye-opening how he managed to teach us with such depth and breadth and simultaneously was continuously emphasizing the acquisition of a biological intuition without having to really even say it outright. He gave us so much of his time and was incredibly flexible and patient with us, redefining things as needed or answering questions we may have asked already but didn't quite grasp, each time with great calmness and kindness and more and more detail. I remember when he was helping me prepare for our presentation, I was nervous and kept forgetting to implement some of the key tips on the way I should present the information, and he was so patient with explaining the presentation advice to me as many times as needed until I was able to really put it in action. The way he helped me improves my presentation skills will stick with me forever, as will the way he taught us such complex concepts in a way that essentially held our hand and walked us through it all step by step in a very digestible way

Likelihood of recommending this course to your peers.

S1: Would definitely recommend!

S2: Very likely.

S3: I am very likely to recommend this course to my peers. As a premed who knew she wanted to be involved in research both during her undergraduate years as well as in the future as she enters the medical field, this fellowship was a great opportunity to learn more about a specific subsection of the field that I am now interested in pursuing in the future as well as gain experience in research related presentations. Additionally, the mentorship I received and the analysis I was able to complete during this course had created a great foundation for the more lab-based research I hope to pursue with mentors in the future as undergrads are able to enter the labs on campus.

S4: I would highly recommend this program to my peers.

S5: I would definitely recommend this course to my peers, but I would hope they are specifically interested in nephrology, not just physiology in general.

S6: I would very much recommend the course to my peers at UChicago.

S7: I still cannot stop raving about it, and I don't plan to stop either. This has been an incredible opportunity and I would definitely recommend it to my peers, in fact I already have numerous times and I will keep doing so. The mentors gave us so much of their time and effort and attention and because of that, it is a research experience I still, many weeks later, rave about to all my family and friends! I genuinely cannot stop talking about how transformative it was for me!

Any other comments.

S2: I wish we could've had the chance to attend some of the zoom clinics with patients. I'm still really interested in the patient interaction aspect of the field. Scheduling was a bit hard sometimes, especially since living with family means that my own schedule was way less flexible.

S3: I don’t have any other specific comments at this time, but thank you to all the doctors who spearheaded this program!

S4: This internship made the most of a very difficult summer for hosting traditional research programs.

S5: No additional comments--I would just like to thank you again for this opportunity! I will hopefully be around in the Section of Nephrology this year and I hope to see you around.

S6: I hope things improve with COVID-19 as I would've loved to also have more hands-on experiences in a laboratory environment. However, I think still being able to analyze data and follow thought-processes was extremely beneficial.

S7: If anything, I feel as though I am not doing the whole program justice by asking all the questions on my mind. I can honestly say, this has been the most cherished experience and I am so so lucky to have been a part of it. And to think all of this good came from an experience that was just online! I simply cannot fathom the joy it would have brought me to take part in it in person with all our peers. This has been a great deal stimulating, for the both the mind and soul (not to sound over dramatic but, quite honestly I don't know how I would have held up without something so fulfilling this summer), and I am extremely grateful to be a part of it. Thank you so so much my mentor and all the amazing doctors for organizing this incredible and comprehensive program and for being an extremely educational and intuitive mentor, you truly were the full embodiment of the word. I can't imagine how difficult it must have been for you all to convert this whole program to an online experience, both logistically, and emotionally, so for all your additional painstaking efforts to meet our needs and teach us with a great deal of patience, understanding, and flexibility, I am extremely grateful. I feel beyond blessed to have been a part of this fellowship.