Pandeylab Bern

16/04/2021

Results of my ongoing collaboration on
"Biased cytochrome P450-mediated metabolism via small-molecule ligands binding P450 oxidoreductase"
involving Shaheena Parween, Patricia Rodríguez Castaño and Natalia Rojas from Bern, Switzerland with the group in Copenhagen involving Nikos Hatzakis Tomas Laursen Sara Thodberg Simon Bo Jensen Flemming Steen Jørgensen Birger Lindberg Møller, and colleagues are now published with Springer Nature in Nature Communications
A key element in human metabolism is P450 oxidoreductase (POR), which donates electrons and selectively activates numerous cytochromes P450 (CYPs) controlling the metabolism of drugs, steroids, and xenobiotics in humans and natural product biosynthesis in plants. We proposed a model of biased metabolism, where ligand binding on POR stabilizes different conformational states that are linked to distinct metabolic outcomes. Biased metabolism may allow designing pathway-specific therapeutics or personalized food suppressing undesired, disease-related, metabolic pathways.
https://www.nature.com/articles/s41467-021-22562-w

10/11/2020

New addition to Pandeylab Bern at Universität Bern

🇨🇭Aquí ven a María Natalia Rojas Velázquez de 🇵🇾Paraguay, actualmente en para su doctorado!

Está abierta la convocatoria anual para las becas de excelencia del gobierno de Suiza!

El gobierno de Suiza ofrece becas para estancias de investigación, doctorados y posdoctorados (posgrados) en universidades suizas, escuelas politécnicas federales y universidades de ciencias aplicadas

Encontrarás más detalles en https://www.eda.admin.ch/countries/uruguay/es/home/dienstleistungen/stipendien.html.

Escríbenos a montevideo@eda.admin.ch para pedir tu paquete de aplicación y entrega tu aplicación hasta finales de noviembre 2020.
.mobility

01/09/2020

New publication from Pediatric Endocrinology lab of
from and

Characterization of Two Novel Variants of the StAR protein related to
https://www.mdpi.com/1422-0067/21/17/6185

Congenital adrenal hyperplasia (CAH) consists of several autosomal recessive disorders that inhibit steroid biosynthesis. We describe a case report diagnosed with adrenal insufficiency due to low adrenal steroids and adrenocorticotropic hormone excess due to lack of cortisol negative feedback signal...

02/07/2020

Three talented international scientists, winner of awards from the Swiss Government Excellence Scholarship will join the Pandey Lab at University Children's Hospital Bern, Switzerland, Department of Biomedical Research, University of Bern. Maria Natalia Rojas Velazquez from the University of Asunción, Paraguay and Mayara Jorgens Prado from the Federal University of Rio Grande do Sur, Brazil, as Ph.D. students. Dr. Shripriya Singh from the Indian Institute of Toxicology Research, of India, will join as a postdoctoral fellow. These scientists will work on steroid hormone disorders, including 21-hydroxylase deficiency, POR deficiency, and congenital adrenal hyperplasia.

30/06/2020

https://www.myscience.org/news/wire/next_generation_sequencing_to_provide_precision_medicine_for_rare_metabolic_disorders-2020-unibe

30.06.2020 - Advances in next-generation-sequencing technology that allow researchers to look at billions of pieces of genetic information are changing the way a disease is diagnosed. Correct identification of changes in the human genetic code responsible for rare metabolic disorders provides scient...

24/06/2020

https://www.mdpi.com/1422-0067/20/18/4606

Turmeric, a popular ingredient in the cuisine of many Asian countries, comes from the roots of the Curcuma longa and is known for its use in Chinese and Ayurvedic medicine. Turmeric is rich in curcuminoids, including curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have potent wou...

24/06/2020

https://www.sciencedirect.com/science/article/pii/S0960076019303462?via%3Dihub

Aromatase (CYP19A1) converts androgens into estrogens and is required for female sexual development and growth and development in both sexes. CYP19A1 …

24/06/2020

https://www.frontiersin.org/articles/10.3389/fphar.2019.01187/full

Cytochromes P450 located in the endoplasmic reticulum require NADPH cytochrome P450 oxidoreductase (POR) for their catalytic activities. Mutations in POR cause multiple disorders in humans related to the biosynthesis of steroid hormones and also affect drug-metabolizing cytochrome P450 activities. E...

24/06/2020

https://academic.oup.com/jcem/article-abstract/105/4/e1272/5736381?redirectedFrom=fulltext

AbstractContext. Mutations in cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We report a novel R550W mutation in PO

24/06/2020

Inhibition of placental CYP19A1 activity remains as a valid hypothesis for 46,XX virilization in P450 oxidoreductase deficiency
https://www.pnas.org/content/early/2020/06/22/2003154117

Cytochrome P450 oxidoreductase deficiency (PORD), caused by mutations in P450 oxidoreductase (POR), is a disorder of steroid metabolism often characterized by disordered sexual development (1⇓–3). POR is required for enzymatic activities of multiple cytochrome P450 enzymes (4). In PNAS, Reisch e...

11/09/2019

Steroid Metabolism in Human Health and Disease
Edited by: Dr. Amit V. Pandey, Inselspital Bern and DBMR Uni Bern.

https://www.mdpi.com/journal/ijms/special_issues/Steroid_Metabolism

IJMS (ISSN 1422-0067).
Deadline : 1 June 2020.

15/07/2019

New Paper from Lab: HIV Drug Efavirenz Inhibits CYP21A2 Activity with Possible Clinical Implications.
BACKGROUND:
The HIV drugs lopinavir and ritonavir have recently been reported to cause transient adrenal insufficiency in preterm newborns. We, therefore, considered HIV drugs as a cause of transiently elevated 17-hydroxyprogesterone (17OHP) levels in a neonatal screening test for congenital adrenal hyperplasia in a preterm girl exposed to zidovudine, efavirenz, tenofovir, and emtricitabine.

OBJECTIVE:
So far, HIV drugs have not been tested for their effect on steroidogenesis and the steroidogenic enzyme activity of CYP21A2 specifically in an in vitro system.

METHODS:
We tested the effect of efavirenz, tenofovir, emtricitabine, and zidovudine on steroidogenesis of human adrenal H295R cells. Cells were treated with the drugs at different concentrations including concentrations in therapeutic use. The effect on CYP21A2 activity was assessed by testing the conversion of radiolabeled 17OHP to 11-deoxycortisol. Cell viability was tested by an MTT assay. In addition, recombinant human CYP21A2 protein was used to assess direct drug effects on CYP21A2 activity.

RESULTS:
We observed significantly decreased CYP21A2 activity in both in vitro testing systems after treatment with efavirenz at therapeutic concentrations. Moreover, efavirenz affected cell viability. By contrast, the other test drugs did not affect steroidogenesis. Follow-up of our patient revealed elevated 17OHP and androgen levels during the first weeks of life, but values normalized spontaneously. Genetic testing for CYP21A2 mutations was negative. Thus, it remains unsettled whether the transient 17OHP elevation in this baby was due to a drug effect.

CONCLUSION:
The HIV drug efavirenz inhibits CYP21A2 activity in vitro through direct interaction with enzyme catalysis at therapeutic concentrations. This may have clinical implications for HIV treatment in children and adults. However, so far, clinical data are scarce, and further studies are needed to be able to draw clinical conclusions.

13/06/2019

New Publication from Paediatric Endocrinology Lab.
Variability in human drug metabolizing cytochrome P450 CYP2C9, CYP2C19... https://www.sciencedirect.com/science/article/pii/S0006291X19310150 …

25/05/2018

http://www.unibe.ch/news/media_news/media_relations_e/media_releases/2018/medienmitteilungen_2018/new_drug_target_to_combat_prostate_cancer/index_eng.html

23/05/2018

https://www.urotoday.com/recent-abstracts/urologic-oncology/prostate-cancer/103995-novel-lead-for-the-design-of-drugs-against-prostate-cancer-and-polycystic-ovary-syndrome-beyond-the-abstract.html?utm_sq=frevqnpfl4&utm_source=twitter&utm_medium=social&utm_campaign=urotoday&utm_content=beyond+the+abstract