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Personal profile

Description of research and teaching

The research projects of the group are related to cancer biology, cell differentiation, and drug discovery and development. Currently, in addition to PI (Hannu Koistinen), one PhD student (Laura Hautala) is working in the group.

Prostatic proteases: 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 7 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.

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.

 

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. The collaborative project in drug development offers a good perspective to drug discovery and development.

Keywords

  • 1182 Biochemistry, cell and molecular biology
  • proteases
  • Kallikreins
  • PSA
  • glycodelin
  • cancer
  • reproduction
  • glycosylation
  • 3122 Cancers
  • proteases
  • prostate cancer
  • 3123 Gynaecology and paediatrics
  • hCG
  • glycodelin
  • 3111 Biomedicine
  • 317 Pharmacy
  • peptides
  • proteases

International and National Collaboration Publications and projects within past five years.

Publications 1994 2019

Glycodelin-A stimulates the conversion of human peripheral blood CD16(-)CD56(bright) NK cell to a decidual NK cell-like phenotype

Lee, C-L., Vijayan, M., Wang, X., Lam, K. K. W., Koistinen, H., Seppälä, M., Li, R. H. W., Ng, E. H. Y., Yeung, W. S. B. & Chiu, P. C. N., Apr 2019, In : Human Reproduction. 34, 4, p. 689-701 13 p.

Research output: Contribution to journalArticleScientificpeer-review

Hyperglycosylated hCG activates LH/hCG-receptor with lower activity than hCG

Koistinen, H., Koel, M., Peters, M., Rinken, A., Lundin, K., Tuuri, T., Tapanainen, J. S., Alfthan, H., Salumets, A., Stenman, U-H. & Lavogina, D., 5 Jan 2019, In : Molecular and Cellular Endocrinology. 479, p. 103-109 7 p.

Research output: Contribution to journalArticleScientificpeer-review

Open Access
File

KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D

Jha, S. K., Jeltsch, M., Rauniyar, K., Chronowska, E., Maina, E., Koistinen, H., Stenman, U. H., Alitalo, K. & Mattonet, K., 17 May 2019, In : eLife. 8, e44478.

Research output: Contribution to journalArticleScientificpeer-review

Open Access
File

Prostate Cancer Risk-Associated Single-Nucleotide Polymorphism Affects Prostate-Specific Antigen Glycosylation and Its Function

PRACTICAl Consortium, Jan 2019, In : Clinical Chemistry (Washington, DC). 65, 1, p. E1-E9 9 p.

Research output: Contribution to journalArticleScientificpeer-review

An immunocapture-LC-MS-based assay for serum SPINK1 allows simultaneous quantification and detection of SPINK1 variants

Ravela, S., Valmu, L., Domanskyy, M., Koistinen, H., Kylänpää, L., Lindström, O., Stenman, J., Hämäläinen, E., Stenman, U-H. & Itkonen, O., Feb 2018, In : Analytical and Bioanalytical Chemistry. 410, 6, p. 1679-1688 10 p.

Research output: Contribution to journalArticleScientificpeer-review

Open Access
File

Prizes

Poul Astrup prize (3rd prize)

Hannu Koistinen (Recipient), 2008

Prize: Prizes and awards

Activities 2000 2014

Member of thesis committee

Hannu Koistinen (Member of thesis committee / follow-up group)
2014

Activity: Examination typesMember of doctoral thesis committee / follow-up group

Member of thesis committee

Hannu Koistinen (Member of thesis committee / follow-up group)
2014

Activity: Examination typesMember of doctoral thesis committee / follow-up group

ASCB Annual Meeting 2014

Hannu Koistinen (Poster Presentation)
2014

Activity: Participating in or organising an event typesOrganisation and participation in conferences, workshops, courses, seminars

Societas Biochemica (External organisation)

Hannu Koistinen (Board member)
2014 → …

Activity: Membership typesMembership or other role in public Finnish or international organization

AACR Annual Meeting 2014, poster presentation

Hannu Koistinen (Poster Presentation)
2014

Activity: Participating in or organising an event typesOrganisation and participation in conferences, workshops, courses, seminars