Cornell University

University of Louisville Research Foundation, Inc.

Repairogen Corp.

Pengbo Zhou

John Olaf Trent

Michael Henry Boice

Frank Borchetta

Chenyi Yang

Albert Cunningham

J David Warren

Described are compositions containing quinones that show activity in enhance DNA repair and/or prevent damage to DNA and/or upregulate genes associated with wound healing. The quinones are thymoquinone, lapachol, myrtucommulone C, or mixtures thereof, and can be formulated into cosmetic compositions for topical administration to a subject in need thereof. The cosmetic compositions can also include sunscreens, surfactants, sunless tanning agents, desquamation agents, antiperspirants, colorants, preservatives and mixtures; and a cosmetically acceptable carrier. The compositions should find use in methods for treating the signs of ageing in mammals, dermatitis and wound healing via topical application to a site in need thereof, such as the skin or hair of the mammals or a wound site.

Cosmetic compositions containing quinones and their topical use on skin and hair

Described are compositions containing quinones that show activity in enhance DNA repair and/or prevent damage to DNA. The quinones are thymoquinone, lapachol, myrtucommulone C, or mixtures thereof, and can be formulated into cosmetic compositions for topical administration to a subject in need thereof. The cosmetic compositions can also include sunscreens, surfactants, sunless tanning agents, desquamation agents, antiperspirants, colorants, preservatives and mixtures; and a cosmetically acceptable carrier. The compositions should find use in methods for treating the signs of ageing in mammals via topical application to the skin or hair of the mammals.

The invention is directed to a method of treating a cancer in an animal and a method of increasing DNA repair activity in an animal. The methods comprise administering to an animal in need thereof an effective amount of a small molecule substance that interferes with the activity of CUL4A, such as a 1,3-benzoxathiol-2-one compound, a pyridine thione compound, a 2,6-diamino-4-thiopyran-3,5-dicarbonitrile compound, or a 1,2,4-triazole-3-thiol compound.

Inhibitors of CRL4 ubiquitin ligase and uses thereof

The current disclosure describes materials and methods for identifying subjects that would benefit from treatment with a DNA topoisomerase 1 inhibitor, based on the levels of cullin 4B gene, RNA and protein levels in the subject. The disclosure identifies CUL4B as a predictive biomarker for cancer diagnosis and the subsequent treatment with directed therapeutic agents. The current disclosure also identifies novel therapeutic agents that modulate the level of CUL4B expression, and sensitize a subject to treatment with a second therapeutic agent.

CUL4B as predictive biomarker for cancer treatment

The present disclosure relates to methods for expansion of stem cell populations using a polypeptide that enhances stem cell growth and proliferation. The present disclosure further relates to novel homeobox protein mutants (e.g., HOXA9 and HOXB4 mutant proteins) and the use thereof to expand certain stem cell populations. The present disclosure also provides methods for treating a subject in need of transplantation of stem cells.

Compositions and methods for the expansion of stem cells

The present invention provides a method of reducing levels of at least one target protein in a cell. The cell is contacted with a first agent and a second agent. The first agent reduces synthesis of the target protein, e.g., by reducing levels of the mRNA of the target protein or inhibits translation of the mRNA. The second agent accelerates degradation of the target protein. The first agent may contact the cell before, after or simultaneously with the second agent. The first agent and the second agent may be in separate delivery vehicles, or in a single delivery vehicle. The first agent may be an RNAi (RNA interference) molecule, such as a small interfering RNA (siRNA), a small hairpin RNA (shRNA) or a microRNA (miRNA). The second agent may be a chimeric polypeptide containing a ubiquitin ligase polypeptide and a target protein interacting domain. The ubiquitin ligase polypeptide can be an E3 ubiquitin ligase, including, but not limited to, an SCF polypeptide, a HECT polypeptide and a UBR1 polypeptide. In one embodiment, the SCF polypeptide is an F-box polypeptide.

Methods for reducing protein levels in a cell

The invention provides methods of preventing or treating a condition associated with DNA damage in an animal comprising the administration of a substance that interferes with the activity of the CUL4A ubiquitin ligase. The invention also provides a substance that interferes with the activity of CUL4A, as well as compositions comprising the interfering substance and a carrier. The substance of the invention preferably enhances nucleotide excision repair activity in an animal. The invention further provides methods of identifying substances that negatively or positively modulate the expression and/or activity of CUL4A.

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Princeton Junction, NJ, United States of America

Pengbo Zhou