Fields of Research

Contact Information

Haartmaninkatu 3 (P.O. Box 21)
FIN-00014 University of Helsinki
Finland
tel. +358 2941 911 (switch)

Alma-intranet

Hannu Koistinen Research Group

The research projects of the group are related to proteases, cancer biology, cell differentiation, and drug discovery and development.

Principal Investigator

Hannu Koistinen, D.Sc., Academy Research Fellow

Group Members

Mykola Domanskyy, Senior Scientist
Johanna Mattsson, PhD
Laura Hautala, Doctoral Student
Kati Räsänen, PhD, Senior Scientist


Functions and targets for treatment of prostate cancer

Prostate cancer is a considerable healthcare problem that causes over 70 000 deaths annually in the EU countries alone and affects the life of 1 of every 8 man. In order to reduce the costs and side effects of treatment and to avoid unnecessary treatment, it is desirable to develop alternative non-invasive therapies and to improve the diagnostic methods.

Proteolytic enzymes (proteases) are useful markers for diagnostics and targets for treatment of prostate cancer. The prostate produces several highly prostate-specific proteases, the most abundant being PSA (KLK3) and hk2 (KLK2), which are potential targets for tumor imaging and treatment. PSA has been shown to reduce angiogenesis and formation of metastases, and hK2 is participating in proteolytic cascades that could promote tumor spread.

We study the functions of these and other proteins, e.g., trypsin and tumor associated trypsin inhibitor (TATI or SPINK1), in prostate and particularly in prostate cancer. We have developed peptides, which modulate the activities of PSA, hK2 and trypsin, and we hypothesize that peptides or peptidomimetic compounds based on these can be used for treatment of prostate cancer. The peptide leads are developed towards drug molecules in an international collaborative project lead by Dr. Koistinen.

This project is planned to be expanded to address the significance of all human proteases, collectively called the degradome, in prostate cancer. To this end novel organotypic models that facilitate high-throuhput RNA-interference based analysis of the effects of proteases will be developed in a collaborative effort.

Interview in International Innovation

International Innovation is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the publication can be found at: www.researchmedia.eu.

 

Left: Structural model showing PSA-inhibitor docked to the active site of the homology model of PSA (The Prostate 2008, 68, 1143-51). Right: 3D pharmacophore model for compounds stimulating PSA-activity (Härkönen et al., ChemMedChem 2011, 6, 2170-8).

 

The role of growth-restricting glycodelin in breast cancer

Glycodelin is a lipocalin family glycoprotein expressed mainly in reproductive tissues. In collaboration with William Yeung's group at University of Honk Kong we have found several reproduction related functions for glycodelin. Interestingly, these functions are regulated by glycodelin's glycosylation, i.e., different glycoforms have different activities.

Currently, the main project is related to glycodelin's role in cell differentiation and breast cancer. We have found that transgenic exression of glycodelin in carcinoma cells results in cell differentiation towards normal and less malignant phenotype. Furthermore, glycodelin reduces tumor growth in a preclinical in vivo model. These findings suggest that glycodelin acts as a tumor suppressor in breast cancer.

Glycodelin-transfection induces cell differentiation and reduces xenograft-tumor growth in mouse mammary fat pads (Hautala et al., Breast Cancer Res Treat 2011, 128, 85-95).


Techniques

Several protein chemistry, molecular biology and cell culture techniques are employed by the group. Group participates in the development of clinical assays for the studied proteins, and drug discovery and development.


Short CV and selected publications


Contact information
:
Hannu Koistinen, D.Sc., Adjunct Professor
PI, Academy Research Fellow
Haartman Institute
Clinical Chemistry
P.O.Box 63 (Haartmaninkatu 8)
Biomedicum Helsinki,
Rm. A424b
FI-00014 University of Helsinki
Finland

Phone:+358 9 471 71734
hannu.k.koistinen (at) helsinki.fi