Biology Education

Current research interests centre for primary health care research (CPF) laboratory

CPF experimental research laboratory is part of Center for primary health care research (https://www.skane.se/en/about-us/research/for-dig-som-forskar/center-for-primary-health-care-research/molecular-family-medicine-laboratory/). It was established with a goal to understand the pathophysiology of common diseases diagnosed in primary health care and to develop diagnostic and prognostic biomarkers for risk assessment and prevention of chronic diseases, commonly diagnosed in primary health care.

Research focus

Our focus is mitochondrial genetic and epigenetic changes, their interaction with nuclear genome, and mitochondrial dysfunction in chronic diseases and aging.

The goal of our research is to identify diagnostic and prognostic biomarkers for common chronic diseases such as cardiovascular diseases, cancer, type 2 diabetes mellitus; mental disorders etc. We use clinical samples such as serum/plasma, biopsies and whole blood for analysis and large databases, which include clinical information on patients.

MSc students

We often have thesis projects for master’s students within the projects conducted in our group. Please, contact Ashfaque Memon (Ashfaque.memon@med.lu.se) or Kristina Sundquist (kristina.sundquist@med.lu.se) or Xiao wang (xiao.wang@med.lu.se) for more details.

https://portal.research.lu.se/en/persons/ashfaque-memon

Contact info: Anna Wendt, anna.wendt@med.lu.se

LU research profile: https://portal.research.lu.se/en/persons/anna-wendt

Start date: Any time between September 2025 and January 2026 (can be discussed)

Length of the project: 45 credits

Project type: master project

Additional information: This project is in collaboration with Jens Largerstedt who will be co supervisor. Link: https://portal.research.lu.se/sv/persons/jens-lagerstedt

Project information:

Aim: The aim of this project is to investigate factors that could regulate the levels of the fatty acid transporter CD36 in insulin producing beta cells.

Hypothesis: We hypothesize that the levels of CD36 in beta cells is regulated by several signals that are strong in obesity and type-2 diabetes such as cytokines (IL4 and IL10) and hyperglycaemia, but also other factors such as microRNAs and medication (dexomethazone). We believe this regulation has an impact on type 2 development especially in obese individuals.

Introduction: Obesity is a strong risk factors for developing type-2 diabetes. There are several mechanisms behind this including the fact that in obese individuals, lipids can accumulate in ectopic tissues such as the liver and skeletal muscles. Type-2 diabetes is the result of both increased insulin resistance and dysfunctional insulin secretion, where ectopic lipid accumulation is a known contributor to insulin resistance. Interestingly, lipids can also wrongfully accumulate in insulin secreting beta cells in the islets causing dysfunctional insulin secretion and even cell death in these cells. We have previously shown that fatty acid transporter CD36 levels are increased in islets from obese individuals with type 2 diabetes. We have also shown that reducing the amount of functional CD36 in the beta cells increase insulin secretion. CD36 is expressed in several tissues in the body and the literature tells us that physiologically, CD36 expression is regulated by different mechanisms in different cell types. In this project we will investigate how CD36 is regulated in the beta cells investigating factors suggested by the literature and our previous studies to be important in CD36 regulation.

Project plan: The experiments in this project will mainly be carried out in the human beta cell line EndoC betaH1 which, like human islets, express CD36.

In our group we have extensive knowledge in investigating microRNA regulation of various proteins. MicroRNAs are short non-coding stretches of RNA that negatively regulate protein expression and thereby play an important role in shaping beta cell function. There are several microRNAs that have been shown to regulate CD36 in other tissues but microRNA regulation of CD36 in beta cells has not been investigated. There are data sets available describing the specific microRNAs expressed in beta cells. As a first step we will cross reference these data sets with known and predicted CD36 specific microRNAs. Candidates from this search will be experimentally tested by overexpressing or downregulating the microRNA in the beta cell line. The effects on CD36 expression can then be determined using qPCR and western blot. To better understand the role of the selected microRNAs we will also investigate the effect of these microRNAs on insulin production and secretion using ELISA.

Depending on the findings and on how much time is left we have the possibility to also investigate how cytokines and pharmaceutical compounds affect CD36 expression. IL-4 is a cytokine that regulates CD36 levels in monocytes. We have previously investigated the role of IL-4 on insulin secretion, but we did not look at the effects on CD36 expression. We still have RNA samples from that study that can be used to investigate CD36 levels in the different treatment groups. Similarly, dexamethasone, a commonly prescribed corticosteroid associated with steroid-induce diabetes, has been linked to CD36 expression. Dexamethasone, again, has been investigated in our group but not in association with CD 36 expression.

Significance: It has been estimated that > 6% of the world’s population live with type-2 diabetes and the numbers continue to rise. One major risk factor for the disease is obesity and it is vital to understand the mechanisms behind obesity-driven type-2 diabetes. This project would help us understand the regulation of lipid influx into the beta cells in health and disease, a knowledge that could be used to treat or, hopefully, prevent beta cell dysfunction in type-2 diabetes.

Contact info: Anna Wendt, anna.wendt@med.lu.se

LU research profile: https://portal.research.lu.se/en/persons/anna-wendt

Start date: Any time between September 2025 and January 2026 (can be discussed)

Length of the project : 45 credits

Project type: master project

Additional information: This project is in collaboration with Lena Eliasson who will be co supervisor. Link: https://www.ludc.lu.se/research/diabetes-islet-cell-exocytosis

 Project information:

Aim: This project aims to examine the role of microRNAs in intra-islet crosstalk. A special focus will be put on exosome-delivered microRNAs and their effects on insulin- and glucagon secretion.

Hypothesis: We hypothesize that microRNA containing extracellular vesicles (EVs) are released from all cell types in the islets of Langerhans. The EVs then travels through the interstitium to neighbouring islet cells, or via the circulation to recipient islet cells further away. Once they reach their designated recipient cells the EVs are taken up in a regulated fashion and the microRNAs can modulate the physiology of the recipient cell. We believe this to be an important, previously unrecognized layer of islet cell regulation.

Introduction: Dysfunctional glucagon and insulin secretion from islet alpha- and beta cells is a hallmark of type-2 diabetes. Given their crucial role in whole body metabolism, both alpha- and beta cells are tightly regulated through several mechanisms including microRNAs. MicroRNAs are short non-coding stretches of RNA that negatively regulate protein expression. We know from work by us and others that they play an important role in beta cell identity and function and the evidence points to an important role for microRNAs in alpha cells too. MicroRNA regulation has previously been assumed to only occur locally within the same cell, but recent publications have demonstrated microRNAs in the circulation both bound to carrier molecules and contained in exosomes (EVs; extra cellular vesicles). The literature shows that EVs can be taken up by recipient cells and regulate their function by delivering their cargo (microRNAs, but also other regulatory proteins). In this project we will investigate local, EV based, microRNA communication within the islets of Langerhans.

Project plan: In the first part of the project, we will investigate microRNAs that are packaged in EVs and released from islet alpha and beta cells. To establish proof of concept we will expose alpha and beta cell lines to biological stress in the form of glucolipotoxic conditions and cytokine treatment (to mimic the diabetic condition) and to standard cell culture conditions (to mimic the healthy state). The growth medium from the cells will then be collected and all EVs released into the media will be purified using exoEasy (Qiagen). The isolated EVs will then be used for two kinds of experiments. Firstly, we will add purified EVs from the mouse beta cell line (stressed or unstressed) to the alpha cell line, or EVs from stressed beta cells to unstressed. We will then investigate secretory capacity (ability to release insulin or glucagon) in the recipient cells using ELISA, insulin/glucagon expression using ELISA and qPCR, cell viability using an MTS assay, and expression of transcription factors with qPCR. The focus will be on hormone secretion and expression and the other experiments will be performed if the time allows.

Secondly, we will isolate microRNAs from the isolated EVs. In a later step we will determine the identity of the microRNAs using small RNA sequencing but for now, if time allows, we will investigate the presence of some candidate microRNAs.

Significance: The potential role of circulating microRNAs as an additional layer of regulation in islet cells is a novel and largely unexplored concept that could provide important insights into diabetes prediction, development, and treatment.