My research focuses on the bone's secretion and renal signaling of the phosphaturic hormone FGF23, using tissue of human nephrectomies assessed as precision-cut kidney slices but also rodent models of chronic kidney disease.

Undergraduate research: During medical school, I investigated mitochondrial morphology under ischemia, and I performed a prospective clinical study that identified a link between extracellular calcium concentrations and vascular stiffness in dialysis patients. This work challenged the dogma that only intracellular calcium affects smooth vascular muscle tone (1). 

Graduate research: The aim of my MD-PhD studies was to determine the mechanism by which a mouse model of Mediator of Cell Motility 1 (Memo1) deficiency developed elevated calcemia (2) resembling Klotho and Fgf23 KO mouse strains. We generated double-transgenic Cre-lox mouse lines and I locally established bone biology methods in the laboratory (micro-computed tomography, primary osteoblast and osteoclast cell culture, bone histology and tissue chemistry analyses) (3–5). Shortly after others found a role for Memo1 in cranial bone mineralization (6), we reported that Memo1 deficiency in mice mimics the human disease hypophosphatasia (4). Further, we found mechanisms by which Memo1 affects mineral homeostasis via gut, intestine and bone, including alterations in magnesium transporters during ubiquitous or kidney-specific Memo deficiency, including hormone treatments and dietary interventions (7,8). With these studies, we advanced the understanding of the redox regulation of ALP dimerization by Memo1 and thus provided a novel molecular explanation and animal model for a human bone disease. Next, I was a co-lead author on a collaborative effort to describe the effects of XPR1 deletion in the murine kidney that led to hypophosphatemic rickets (9). For this work, I planned and performed all structural bone analyses and prepared bone for histomorphometric analysis. This study has characterized the first putative basolateral phosphate efflux protein in the mouse kidney, two decades after the apical phosphate transport proteins were identified. Our study has thus given a pivotal advance to the field and sparked wide interest and further investigations in XPR1.

Junior group leader – basic science: Using a Young Investigator Award from the National Competence Centre of Research – Kidney.CH, I have co-supervised a PhD project at the University of Bern. We investigated the bone-specific role of Memo1 in experimental kidney injury (10). We also deciphered mechanisms by which redox protein Memo1 promotes FGF23-driven cell signaling in the kidney by redox proteomics, biochemical profiling and cell-free redox protein biochemistry analyses as well as transcriptomics, primary renal cell culture and mouse physiology (11). FGF23 triggers a cascade of oxidative post-translational protein modifications associated with an altered activity of redox-controlled protein tyrosine phosphatases. This is one of the first studies demonstrating a connection between FGF23 and redox signaling in the kidney and it is bound to attract more research given that redox homeostasis is deeply disturbed during CKD (12).  Finally, since my recent moving to Karolinska Institutet, Stockholm as a visiting scientist, I have been working with CKD mouse models and precision-cut kidney slices (PCKS) as an experimental ex vivo system to study FGF23 signaling and to mimic kidney transplantation, respectively. 

Clinical studies: In addition to my fundamental studies, I have performed clinical studies at University Hospital of Bern. I have developed skills in database management and advanced statistical analyses/modelling, but also in patient recruitment and closely interacting with the local ethics committee. I have performed analyses of muscular mass in patients with CKD-MBD and other diseases (co-first author manuscript submitted), I am the analysis leader of a recently completed 12-year Renal Osteodystrophy Registry Study at University Hospital Bern (analyses ongoing). We have found robust associations between FGF23 and aldosterone metabolism in a large registry of renal patients, linking two hormone systems that have major adverse impact on cardiac and renal health in CKD (13). I have also taken an active role in prospective COVID-19 related studies and one meta-analysis, to assist vaccination strategies in vulnerable populations. I have published one highly cited COVID-19 vaccination study as first author (14) and 3 studies as last/co-last author (15–17). Our  studies have been cited by health authorities and have potential impact on the planning of vaccination strategies. These vaccination studies were very competitive clinical research work conducted on an efficient timescale, and they demonstrate my ability to rapidly establish and manage successful research collaborations.

Future research: My future research will focus on the bone's secretion and the signaling of FGF23 using tissue of human nephrectomies assessed as precision-cut kidney slices but also rodent models of chronic kidney disease. Additional study focus are mouse genetics and human patient collectives with CKD-MBD.
 
These approaches will combine my expertise in bone research methods with  experimental kidney disease models, precision-cut kidney slices, patient studies and omics techniques.
 
 I expect that this research will contribute to the molecular understanding of the mineral and bone disorders that frequently occur during chronic kidney disease and make patients vulnerable for high morbidity due to vascular calcification and accelerated fractures.                                                

References
1.          Moor MB, Kruse A, Uehlinger DE, Eisenberger U. Arterial stiffness depends on serum ionized calcium levels during dialysis with regional citrate anticoagulation. Artif Organs. 2013 May;37(5):467–74. 

2.          Haenzi B, Bonny O, Masson R, Lienhard S, Dey JH, Kuro-o M, et al. Loss of Memo, a novel FGFR regulator, results in reduced lifespan. FASEB J Off Publ Fed Am Soc Exp Biol. 2014 Jan;28(1):327–36. 

3.          Albano G, Moor M, Dolder S, Siegrist M, Wagner CA, Biber J, et al. Sodium-dependent phosphate transporters in osteoclast differentiation and function. PloS One. 2015;10(4):e0125104. 

4.          Moor MB, Ramakrishnan SK, Legrand F, Dolder S, Siegrist M, Durussel F, et al. Redox-Dependent Bone Alkaline Phosphatase Dysfunction Drives Part of the Complex Bone Phenotype in Mice Deficient for Memo1. JBMR Plus. 2018 Jul;2(4):195–205. 

5.          Moor MB, Haenzi B, Legrand F, Koesters R, Hynes NE, Bonny O. Renal Memo1 Differentially Regulates the Expression of Vitamin D-Dependent Distal Renal Tubular Calcium Transporters. Front Physiol. 2018;9:874. 

6.          Van Otterloo E, Feng W, Jones KL, Hynes NE, Clouthier DE, Niswander L, et al. MEMO1 drives cranial endochondral ossification and palatogenesis. Dev Biol. 2016 15;415(2):278–95. 

7.          Moor MB, Ramakrishnan SK, Legrand F, Bachtler M, Koesters R, Hynes NE, et al. Elevated serum magnesium lowers calcification propensity in Memo1-deficient mice. PloS One. 2020;15(7):e0236361. 

8.          Moor MB, Bonny O. Memo1 gene expression in kidney and bone is unaffected by dietary mineral load and calciotropic hormones. Physiol Rep. 2020 Apr;8(7):e14410. 

9.          Ansermet C, Moor MB, Centeno G, Auberson M, Hu DZ, Baron R, et al. Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron. J Am Soc Nephrol JASN. 2017 Apr;28(4):1073–8. 

10.        Bartos K, Moor MB. FGFR regulator Memo1 is dispensable for FGF23 expression by osteoblasts during folic acid-driven kidney injury. Physiol Rep. 2023 Mar;11(6):e15650. 

11.        Bartos K, Ramakrishnan SK, Braga-Lagache S, Hänzi B, Durussel F, Prakash Sridharan A, et al. Renal FGF23 signaling depends on redox protein Memo1 and promotes orthovanadate-sensitive protein phosphotyrosyl phosphatase activity. J Cell Commun Signal. 2022 Nov 25; 

12.        Ebert T, Neytchev O, Witasp A, Kublickiene K, Stenvinkel P, Shiels PG. Inflammation and Oxidative Stress in Chronic Kidney Disease and Dialysis Patients. Antioxid Redox Signal. 2021 Dec 10;35(17):1426–48. 

13.        Moor MB, Dhayat NA, Schietzel S, Grössl M, Vogt B, Fuster DG. Urinary tetrahydroaldosterone is associated with circulating FGF23 in kidney stone formers. Urolithiasis. 2022 Jun;50(3):333–40. 

14.        Moor MB, Suter-Riniker F, Horn MP, Aeberli D, Amsler J, Möller B, et al. Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study. Lancet Rheumatol. 2021 Nov;3(11):e789–97. 

15.        Schietzel S, Anderegg M, Limacher A, Born A, Horn MP, Maurer B, et al. Humoral and cellular immune responses on SARS-CoV-2 vaccines in patients with anti-CD20 therapies: a systematic review and meta-analysis of 1342 patients. RMD Open. 2022 Feb;8(1):e002036. 

16.        Sidler D, Born A, Schietzel S, Horn MP, Aeberli D, Amsler J, et al. Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy. RMD Open. 2022 Mar;8(1):e002166. 

17.        Toepfner N, von Meißner WCG, Strumann C, Drinka D, Stuppe D, Jorczyk M, et al. Comparative Safety of the BNT162b2 Messenger RNA COVID-19 Vaccine vs Other Approved Vaccines in Children Younger Than 5 Years. JAMA Netw Open. 2022 Oct 18;5(10):e2237140–e2237140.